The UB team is formed by José Pablo Rivas-Fernández, first author of the article, and Carme Rovira, ICREA research professor, both from the UB’s Faculty of Chemistry and the UB Institute of Theoretical and Computational Chemistry (IQTCUB), in coordination with Casper Wilkens, biotechnologist at the Technical University of Denmark (DTU). Experts from the Norwegian University of Science and Technology (NTNU) and North Carolina State University (United States) have also participated.

Despite the abundance of alginates in the marine environment, their range of opportunities, especially in the biomedical sector, is severely limited by the inhomogeneity of their composition in the natural state — they may contain a mixture of mannuronic acid and guluronic acid sugars in varying proportions. Knowledge of the mechanism of action of AL enzymes when they specifically break the bonds connecting the mannuronic acid-type sugars in this polymer will help to overcome these limitations. “The results lay the groundwork for manipulating these enzymes and designing variants with better catalytic properties and higher efficiency on a large scale.

By using industrial techniques and bioprocesses, it will be possible to optimize the production of ‘tailored alginates’ in sufficient quantities to meet society’s needs,” the researchers explain. “These findings will also allow for a “better use of natural resources and boost the green economy by using enzymes as key tools in the production of these alginates,” say the authors.

Computational analysis with the MareNostrum 5 supercomputer

Part of the study was based on the computational analysis of the action mechanism of these enzymes, using as a starting point the three-dimensional structures of the AL enzyme in interaction with different alginate variants, obtained by the DTU collaborators. Based on this structure and using the resources of the MareNostrum 5 supercomputer at the Barcelona Supercomputing Center — Centro Nacional de Supercomputación (BSC-CNS), the UB team has carried out molecular dynamics simulations, using multiscale quantum mechanics and molecular mechanics techniques to model and obtain a detailed description at the atomic level of the chemical reaction that takes place during the degradation of alginates.

These simulations have reconciled previous scientific discrepancies about the number of stages in which the reaction occurs, confirming that it happens in a single stage and that the polymer breaks at the centre, not at one end. They have also cleared the nature of the transition state — the highest energy configuration during the reaction — as a highly negatively charged species. “This finding suggests that we may be able to control at what point the polymer breaks down by mutations of certain amino acids in the enzyme’s active centre,” the researchers explain.

Another important element of the study is that the enzymes analysed belong to family 7 of lyases, the most abundant known to date, which allows extrapolating the mechanism described to other enzymes with high biotechnological potential.

These findings also facilitate the identification of key residues or amino acids that can be targeted to improve the efficiency of these enzymes, a very promising line of research on which the UB team is already working.

Moreover, the results improve the understanding of the chemical evolution of alginate during its degradation, a fundamental element for the design of probes capable of identifying and isolating alginate lyases, which have not yet been described. In this sense, UB researchers are currently working on the design of probes that allow the efficient identification of new enzymes active in carbohydrates.

This study is part of Carbocentre, a project funded by a Synergy Grant from the European Research Council (ERC).

Virginia Tech researchers have gained a better understanding of this insidious virus by studying its rodent hosts in North America. Using National Science Foundation data, they found three hotspots of hantavirus circulation in wildlife — Virginia, Colorado, and Texas — and identified 15 rodent species as carriers, including six species that had not previously been identified as hosts of the virus.

The details of their study was published in Ecosphere.

“This project is timely because hantavirus is considered an emerging disease of pandemic potential with symptoms that resemble severe COVID-19 infections,” said Paanwaris Paansri, a Ph.D. student in the Department of Fish and Wildlife Conservation and co-author of the study.

Hantaviruses are a family of viruses that have been identified in regions all over the globe and can reach mortality rates similar to other diseases of high concern, such as nipah and Ebola. In Asia, hemorrhagic fever with renal syndrome is caused by the Hantaan virus, in Europe that syndrome is caused by the Dobrava-Belgrade virus, and in North and South America, hantavirus pulmonary syndrome is caused by Sin Nombre virus and Andes virus — all hantaviruses. Sin Nombre virus was first discovered in New Mexico in 1993.

Little is known about the ecology of hantaviruses in wildlife except that the pathogen is spread to humans by inhalation of aerosolized excreta, urine, or saliva from asymptomatic rodent hosts, and it can be fatal in humans.

The Virginia Tech team used data from the National Science Foundation’s National Ecological Observatory Network program to gain a better understanding of hantavirus circulation in its sylvatic cycle — the pathogen’s life cycle in wildlife — by examining the environmental influences and geographical distribution of the rodent hosts. The program collected and tested 14,004 blood samples from 49 species at 45 field sites across the United States from 2014-19.

“In North America, Peromyscus maniculatus, the deer mouse, is the most common carrier but our study also revealed that other rodent species have a higher prevalence of hantavirus, which changes the current paradigm in hantavirus circulation in wildlife,” said Paansri, whose mentor Associate Professor Luis E. Escobar, led the study and is an affiliate with the Fralin Life Sciences Institute. “This new information is expected to help us understand where and when hantavirus is most likely to occur, which is crucial for predicting outbreaks and informing public health officials.”

The discovery of six new rodent species of hantavirus hosts is significant. Some of these newly discovered hosts inhabit regions where traditional hosts, such as the deer mouse or the white-footed mouse (Peromyscus leucopus), are absent, meaning they could be potential reservoirs of the virus in new or overlooked areas.

“This expands our understanding of the basic biology of the virus and shows that the virus is more adaptable than previously believed,” Paansri said. “This has direct implications for surveillance strategies and risk assessments and can help explain some cases of hantavirus in humans where the main reservoir is absent or rare.”

In addition to expanding the known host species, the researchers were able to gain a better understanding of seasonal trends and effects of seasonal weather shifts. For example, warmer winters and increased precipitation can increase rodent populations and drier conditions can facilitate the generation of contaminated dust containing particulates from rodent excrement and saliva, increasing the risk of transmission to humans.

“Climate change can cause population increases or distributional shifts of rodents, altering the epidemiology of hantavirus,” Paansri said. “These fluctuations can lead to more frequent rodent-human interactions and increase the chance of spillover. We found some evidence that rodent demography and hantavirus prevalence can be predicted months in advance.”

The actual number of human cases of hantavirus infections is largely unknown, according to Paansri, because many infections remain silent, meaning the infected individual may not develop any symptoms or the symptoms could mirror other diseases, such as the common cold or influenza.

The researchers plan to further explore the extent to which climatic variations influence hantavirus transmission in wildlife and in humans..

“We believe that many lessons learned from this study can be generalized to other wildlife diseases, considering that their distribution is global,” Paansri said.

Abdelghafar Alkishe, a Virginia Tech 2022-23 presidential postdoctoral fellow, also worked on this study.

AML patients are often treated using allogeneic hematopoietic stem cell transplantation (allo-HCT), where they receive stem cells from a donor. Unfortunately, despite advancements with allo-HCT, many AML patients relapse.

In a recent article published in Nature Cancer, a multi-institutional research team led by The University of Osaka describes how a molecule called HLA-DRB1 can be used as a target for chimeric antigen receptor (CAR)-based therapy for AML. In CAR-based therapy, T cells are engineered to target and kill cells that express a specific molecule. CAR T cells have been highly successful in individuals with B cell leukemia/lymphoma and multiple myeloma (MM). However, most of the CAR T cell targets currently in clinical trials for AML are also expressed in normal cell types, leading to potential toxicity.

“In our previous work in MM, we screened monoclonal antibodies (mAbs) to identify any that could react with human MM samples but not with normal blood cells,” says Shunya Ikeda, lead author of the study. “We aimed to use that same strategy to find AML-specific antigens.”

The team began screening thousands of mAbs raised against AML cells, narrowing this list down to 32 that bind specifically to AML cells. One mAb, named KG2032, clearly bound to AML cells in over 50% of patient samples tested. Using a sequencing strategy, the researchers determined that KG2032 bound to HLA-DRB1.

“Interestingly, we found that KG2032 reacted with a specific HLA-DRB1 subset in which the protein has an amino acid other than aspartic acid in the 86^th position,” explains Naoki Hosen, senior author of the article. “KG2032 would therefore only be reactive to AML cells in individuals with mismatched HLA-DRB1, meaning the patient carries this amino acid residue but the allo-HCT donor does not.”

This finding indicates that HLA-DRB1 can be a potential target in treating certain patients with AML who have relapsed after allo-HCT.

The team then engineered KG2032 CAR T cells without the reactive HLA-DRB1 allele to test this finding. The KG2032 CAR T cells displayed strong and specific anti-AML effects in vitro with cell culture experiments, as well as in vivo with a mouse model. The treated mice did not display any overt signs of toxicity. Engineered cord blood-derived CAR natural killer (NK) cells showed similar results.

Overall, these very promising findings indicate that KG2032-derived CAR T or NK cells may be a lifesaving intervention for AML patients who have relapsed following allo-HCT. Clinical trials are currently being planned for both cell types.

This was true of the black hole at the heart of SDSS1335+0728, a distant and unremarkable galaxy 300 million light-years away in the constellation of Virgo. After being inactive for decades, it suddenly lit up and recently began producing unprecedented flashes of X-ray light.

The first signs of activity appeared in late 2019, when the galaxy unexpectedly began shining brightly, attracting the attention of astronomers. After studying it for several years, they concluded that the unusual changes they saw were probably the result of the black hole suddenly ‘switching on’ — entering an active phase. The bright, compact, central region of the galaxy is now classified as an active galactic nucleus, nicknamed ‘Ansky’.

“When we first saw Ansky light up in optical images, we triggered follow-up observations using NASA’s Swift X-ray space telescope, and we checked archived data from the eROSITA X-ray telescope, but at the time we didn’t see any evidence of X-ray emissions,” says Paula Sánchez Sáez, a researcher at the European Southern Observatory, Germany, and leader of the team that first explored the black hole’s activation.

Ansky wakes up

Then, in February 2024, a team led by Lorena Hernández-García, a researcher at the Valparaiso University, Chile, began to see bursts of X-rays from Ansky at nearly regular intervals.

“This rare event provides an opportunity for astronomers to observe a black hole’s behaviour in real time, using X-ray space telescopes XMM-Newton and NASA’s NICER, Chandra and Swift. This phenomenon is known as a quasiperiodic eruption, or QPE. QPEs are short-lived flaring events. And this is the first time we have observed such an event in a black hole that seems to be waking up,” explains Lorena.

“The first QPE episode was discovered in 2019, and since then we’ve only detected a handful more. We don’t yet understand what causes them. Studying Ansky will help us to better understand black holes and how they evolve.”

“XMM-Newton played a pivotal role in our study. It is the only X-ray telescope sensitive enough to detect the fainter X-ray background light between the bursts. With XMM-Newton we could measure how dim Ansky gets, which enabled us to calculate how much energy Ansky releases when it lights up and starts flashing.”

Unravelling puzzling behaviour

The gravity of a black hole captures matter that gets too close and can rip it apart. The matter from a captured star, for example, would be spread into a hot, bright, rapidly spinning disc called an accretion disc. Current thinking is that QPEs are caused by an object (that could be a star or a small black hole) interacting with this accretion disc and they have been linked to the destruction of a star. But there is no evidence that Ansky has destroyed a star.

The extraordinary characteristics of Ansky’s recurring bursts prompted the research team to consider other possibilities. The accretion disc could be formed by gas captured by the black hole from its neighbourhood, and not a disintegrated star. In this scenario, the X-ray flares would be coming from highly energetic shocks in the disc, provoked by a small celestial object travelling through and disrupting the orbiting material, repeatedly.

“The bursts of X-rays from Ansky are ten times longer and ten times more luminous than what we see from a typical QPE,” says Joheen Chakraborty, a team member and PhD student at the Massachusetts Institute of Technology, USA.

“Each of these eruptions is releasing a hundred times more energy than we have seen elsewhere. Ansky’s eruptions also show the longest cadence ever observed, of about 4.5 days. This pushes our models to their limits and challenges our existing ideas about how these X-ray flashes are being generated.”

Watching a black hole in action

Being able to watch Ansky evolving in real time is an unprecedented opportunity for astronomers to learn more about black holes and the energetic events they power.

“For QPEs, we’re still at the point where we have more models than data, and we need more observations to understand what’s happening,” says ESA Research Fellow and X-ray astronomer, Erwan Quintin.

“We thought that QPEs were the result of small celestial objects being captured by much larger ones and spiralling down towards them. Ansky’s eruptions seem to be telling us a different story. These repetitive bursts are also likely associated with gravitational waves that ESA’s future mission LISA might be able to catch.”

“It’s crucial to have these X-ray observations that will complement the gravitational wave data and help us solve the puzzling behaviour of massive black holes.”

The study, led by the Swedish University of Agricultural Sciences, revealed that commonly detected environmental levels of clobazam — a medication often prescribed for sleep disorders — increased the river-to-sea migration success of juvenile salmon in the wild.

The researchers also discovered that clobazam shortened the time it took for juvenile salmon to navigate through two hydropower dams along their migration route — obstacles that typically hinder successful migration.

Dr Marcus Michelangeli from Griffith University’s Australian Rivers Institute, who was a key contributor to the study published in Science, emphasised the increasing threat of pharmaceutical pollution to wildlife and ecosystems worldwide.

“Pharmaceutical pollutants are an emerging global issue, with over 900 different substances having now been detected in waterways around the world,” Dr Michelangeli said.

“Of particular concern are psychoactive substances like antidepressants and pain medications, which can significantly interfere with wildlife brain function and behaviour.

Dr Michelangeli noted that the study’s real-world focus sets it apart from previous research.

“Most previous studies examining the effects of pharmaceutical pollutants on wildlife have been conducted under controlled laboratory conditions, which don’t fully capture the complexities of natural environments,” he said.

“This study is unique because it investigates the effects of these contaminants on wildlife directly in the field, allowing us to better understand how exposure impacts wildlife behaviour and migration in a natural context.

“While the increased migration success in salmon exposed to clobazam might seem like a beneficial effect, it is important to realise that any change to the natural behaviour and ecology of a species is expected to have broader negative consequences both for that species and the surrounding wildlife community.”

The research team employed innovative slow-release pharmaceutical implants and animal-tracking transmitters to monitor how exposure to clobazam and the opioid painkiller tramadol — another common pharmaceutical pollutant — affected the behaviour and migration of juvenile Atlantic salmon (Salmo salar) in Sweden’s River Dal as they migrated to the Baltic Sea.

A follow-up laboratory experiment also found that clobazam altered shoaling behaviour, indicating that the observed migration changes in the wild may result from drug-induced shifts in social dynamics and risk-taking behaviour.

Dr Michelangeli explained that predicting the full extent of these impacts remains challenging

“When you consider realistic exposure scenarios where entire ecosystems are exposed — encompassing multiple species and a diversity of contaminants — the potential consequences become even more complex,” he said.

While the recent decline of Atlantic salmon is primarily attributed to overfishing, habitat loss, and fragmentation — leading to their endangered status — the study highlights how pharmaceutical pollution could also influence key life-history events in migratory fish.

Dr Michelangeli pointed out that many pharmaceuticals persist in the environment due to poor biodegradability and insufficient wastewater treatment. However, there is hope.

“Advanced wastewater treatment methods are becoming more effective at reducing pharmaceutical contamination, and there is promising potential in green chemistry approaches,” he said.

“By designing drugs that break down more rapidly or become less harmful after use, we can significantly mitigate the environmental impact of pharmaceutical pollution in the future.”

The study ‘Pharmaceutical pollution influences river-to-sea migration in Atlantic salmon (Salmo salar)’ has been published in Science.

Autoimmune diseases are often chronic conditions that affect up to ~15 million people in the U.S. and up to 12% of the global population. CAR-T cell therapy has demonstrated curative potential in select autoimmune diseases by creating a system-wide immune ‘reset’, improving a patient’s quality of life, and reducing the need for life-long immune suppressants. However, conventional CAR-T cell therapies require lymphodepletion — a chemotherapy procedure used to eliminate existing immune cells to ensure the CAR-T cells can effectively expand. Further, this procedure can lead to increased risk of infection and severe side effects. CLBR001 + SWI019 was designed to avoid these issues by eliminating the need for lymphodepletion, reducing side effects and potentially making treatment accessible to a broader patient population.

“Patients with chronic autoimmune diseases need curative options that do not require life-long immunosuppressive therapy to manage their condition,” says Travis Young, vice president of biologics at Calibr-Skaggs. “Our CLBR001 + SWI019 cell therapy has the potential to transform the treatment paradigm for patients by eliminating chemotherapy-associated risks.”

Calibr-Skaggs’ Chief Medical Officer Chan Beals says, “Successfully establishing safety and efficacy of CLBR001 + SWI019 for conditions like lupus and rheumatoid arthritis could pave the way for broader therapeutic use in other autoimmune diseases, offering new hope to many more patients in the future.”

Patient enrollment for the clinical trial is anticipated to begin soon.

About CLBR001 + SWI019 Switchable CAR-T

Calibr-Skaggs’ CLBR001 + SWI019 switchable CAR-T cell therapy differs from conventional CAR-T approaches by leveraging two components, a sCAR-T cell (CLBR001) and a protein-based biologic “switch” (SWI019) that targets CD19-positive B cells. CLBR001 + SWI019 has already demonstrated promising results in treating patients with B cell malignancies, with the ability to shorten the duration of adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and preclinical work has demonstrated the unique ability to work without lymphodepletion. In early-stage trials, CLBR001 cells expanded in patients to higher levels in peripheral blood compared to approved CAR-T cell products, with robust persistence.

“This is an important insight into how people who lived in this region were living and hunting and responding to their environment,” says Sara Watson, a postdoctoral scientist at the Field Museum’s Negaunee Integrative Research Center and lead author of the study.

During the period when these blades were made, between 24,000 and 12,000 years ago, the Earth was nearing the end of the last major ice age. Since so much of the Earth’s water was frozen in glaciers and ice caps, the sea level was lower, and the region that’s now the coast of South Africa was a few miles inland. “Instead of being right on the water like they are today, these caves would have been near vast, open plains with large game animals like antelope,” says Watson. “People hunted those animals, and to do that, they developed new tools and weapons.”

The caves, part of what archaeologists call the Robberg technocomplex, no longer overlook a plain — they’re in a towering cliff face over a rocky beach. “It’s a 75-foot climb up to the cave from the shoreline,” says Watson. “We had safety ropes and a staircase made of sandbags, and we had to be harnessed in while doing the excavation.”

Every day, Watson and her colleagues made the climb with all their excavation and photography equipment, weighing up to 50 pounds per person. “Since these are extremely, extremely old sites, from before the end of the last ice age, we had to be very careful with our excavation,” says Watson. “We used little tiny dental tools and mini trowels so that we could remove each little individual layer of sediment.”

Beneath ancient dust and dirt, Watson and her team found thousands of stone tools: small, sharp blades, as well as the larger pieces of rock from which these blades were chipped. The bigger rock that blades are made from is called a core. “When your average person thinks about stone tools, they probably focus on the detached pieces, the blades and flakes. But the thing that is the most interesting to me is the core, because it shows us the particular methods and order of operations that people went through in order to make their tools,” says Watson.

Watson and her colleagues observed several distinct patterns of how the cores had been broken into smaller blades. “In a lot of these technologies, the core reduction is very specific, and it’s something that you are taught and learn, and that’s where the social information is,” says Watson. “If we see specific methods of core reduction at multiple sites across the landscape, as an archaeologist, it tells me that these people were sharing ideas with one another.”

For instance, one particular method of breaking tiny bladelets off of a core that Watson found in the Robberg caves is a style also found hundreds of miles away in places including Namibia and Lesotho. “Same core reduction pattern, same intended product,” says Watson. “The pattern is repeated over and over and over again, which indicates that it is intentional and shared, rather than just a chance similarity.”

Overall, Watson says that the study reveals how much there still is to learn about the Robberg caves and the people who used them thousands of years ago. “We have a very long and rich history as a species, and humans go back a lot farther in time than most people realize,” says Watson. “People living around the last ice age were very similar to people today.”

The study, led by the University of East Anglia (UEA), examined the relationship between the extent of the climatic conditions that species tolerate and in which populations can survive — known as climatic niche breadth — and their likelihood of declining in response to climate change.

For species inhabiting a similar area of geographic space, those able to tolerate a wider range of climate conditions are less likely to experience population declines, and are more likely to be increasing, compared to those with narrower climatic preferences.

The authors say their findings, published in the Journal of Biogeography, provide valuable insights into how climatic niche breadth can act as an important factor in predicting bird species vulnerability to climate change.

They suggest incorporating species’ climatic niches into climate change risk assessments to better inform conservation strategies, arguing that variation in climatic conditions within a species range can provide greater nuance in understanding their resilience to factors that affect their population.

“Deciding which species are more at risk isn’t straight forward, and species may be declining for a range of reasons,” said lead author Karolina Zalewska, a postgraduate researcher in UEA’s School of Environmental Sciences.

“Rare species and those that have smaller distributions are more likely to be vulnerable to climate change. This study has shown that birds that are more widespread, such as the house sparrow and the common starling, can also face threats to their populations.

“Species, whether rare or widespread, with narrower climatic niches may be more susceptible to the rapid changes brought on by climate change compared to those with broader niches, and this may be one of the underlying reasons behind the population declines observed.

“Our results emphasise the importance of understanding and incorporating the level of exposure to climatic variability when assessing vulnerability to climate change and long-term population declines.”

Human-induced climate change has increasingly been identified as a major threat to global biodiversity. However, the extent of this threat is likely to be uneven across species, due to differences in life histories or exposure to environmental change, with some climatic conditions, such as variables of temperature and rainfall, being more widespread than others across geographic area.

While species with broad geographic distributions would be expected to experience a wider range of climatic conditions and so be more resilient to environmental change, recent population declines of many widespread species suggest other factors may be involved, with the breadth of climatic conditions a species experiences being a possible indicator of their resilience to climate change.

Co-author Prof Aldina Franco, also from the School of Environmental Sciences, said: “Faced with the challenges of the global biodiversity crisis and climate change, the rapid assessment of species vulnerability to environmental change has become of paramount importance to address priorities for conservation. As climate change accelerates, our study highlights the need to prioritize species that are most at risk due to their more restricted environmental requirements.”

The researchers drew on data for the population trends of 159 European breeding bird species across 29 European countries from the Pan-European Common Bird Monitoring Scheme. These 40-year population trends were related to the climate conditions species experience and their distribution area.

They used 30-years of climate data for the species breeding ranges to construct representations of their climatic niches and produced a new index of climatic niche breadth that accounts for species distribution area.

This analysis, along with additional factors such as the species’ diet, primary habitat type, migratory status, and average body mass, was then used to explore how these variables influence the long-term population trends.

“These findings can help us understand the threats associated with climate change and allow for rapid assessment of the importance of climatic factors on population trends, providing an invaluable tool for targeting species conservation,” added Miss Zalewska. “In particular, we show that the climatic niche breadth to range area index can help predict which species may be more vulnerable to population declines.”

Within the species included in this study, 58 had a decreasing population trend, populations of 68 species were stable and 33 were increasing.

As in previous studies the team found that species associated with farmland habitats, both in the UK and wider European area, such as the corn bunting or skylark, were more likely to be declining while those able to tolerate human-modified environments, including blackbirds and blue tits, were more likely to experience increasing population trends.

The work was supported by funding from the UK’s Natural Environment Research Council and the ARIES Doctoral Training Partnership.