Bee study: Both habitat quality and biodiversity can impact bee health

Efforts to promote the future health of both wild bees and managed honeybee colonies need to consider specific habitat needs, such as the density of wildflowers.

At the same time, improving other habitat measures -- such as the amount of natural habitat surrounding croplands -- may increase bee diversity while having mixed effects on overall bee health.

Those are the key findings from a new analysis of several thousand Michigan bees from 60 species. The study looked at how the quality and quantity of bee habitat surrounding small farm fields affects the levels of common viral pathogens in bee communities.

"Future land management needs to consider that broadly improving habitat quality to benefit pollinator community diversity may not necessarily also benefit pollinator health," said University of Michigan biologist Michelle Fearon, lead author of a study published online Nov. 30 in the journal Ecology. The other authors are from U-M and the University of Washington.

"To promote pollinator health, we need to focus on improving specific habitat quality features that are linked to reducing pathogen prevalence, such as planting greater density of flowers," said Fearon, a postdoctoral fellow in the Department of Ecology and Evolutionary Biology.

Bees are indispensable pollinators, supporting both agricultural productivity and the diversity of flowering plants worldwide. But in recent decades, both native bees and managed honeybee colonies have seen population declines, which are blamed on multiple interacting factors including habitat loss, parasites and disease, and pesticide use.

As part of the work for her U-M doctoral dissertation, Fearon and her colleagues netted and trapped more than 4,900 bees at 14 winter squash farms in southeastern Michigan, where both honeybees and wild native bees pollinate the squash flowers.

The bees were analyzed for the presence of three common viral pathogens. Consistently, lower virus levels were strongly linked to greater species richness, or biodiversity, among local bee communities. The number of bee species at each farm ranged from seven to 49.

Those findings, published in February 2021 in Ecology, provided support for what ecologists call the dilution effect. This controversial hypothesis posits that increased biodiversity can decrease, or dilute, infectious disease transmission.

But an unresolved question lingered after that study was published: Was biodiversity truly responsible for the observed reductions in viral levels, or was there something about habitat quality that drove changes in both bee biodiversity and viral pathogen prevalence?

"Many studies have shown that high-biodiversity communities are ones with low rates of infectious disease. But we also know that better habitat quality often leads to greater biodiversity," said study co-author Chelsea Wood of the University of Washington, a former Michigan Fellow at U-M.

"So which factor is actually driving down disease risk: biodiversity or habitat? Do high-biodiversity communities dilute disease prevalence? Or do communities in high-quality habitat have healthier hosts, who are better at resisting infection? Our data show that some apparent 'dilution effects' could actually have nothing at all to do with biodiversity."

Previous studies have demonstrated that habitat factors can directly influence both an animal's nutritional status and the strength of its immune system, which in turn can influence its susceptibility to pathogens. For example, Eurasian red squirrels living in fragmented habitats host greater gastrointestinal parasite burdens than those living in continuous forest habitats.

To get to the root cause of their Michigan bee observations, Fearon and her co-authors generated models allowing them to rigorously disentangle the effects of habitat characteristics on patterns of pathogen prevalence.

They reexamined the previously collected bee data and added new information about local and landscape-level habitat. For the study, the researchers defined high-quality bee habitat as areas that provide sufficient quantity and diversity of floral resources (both pollen and nectar) to sustain good pollinator nutrition.

At the local level, floral richness (meaning flower species diversity) and floral density were the key indicators of high-quality habitat. At the landscape level, proportion of "natural areas" surrounding farm fields and landscape richness (meaning areas with more land cover types) were the key characteristics. Natural areas included deciduous, evergreen and mixed forest; herbaceous and woody wetland; shrubland; grass pasture; and wildflower meadow.

The researchers found that habitat can have both positive and negative impacts on pathogen levels in bee communities. This is evidence for what the authors called a habitat-disease relationship, where habitat quality has a direct impact on bee health.

In general, a higher proportion of natural area and a greater richness of land cover types were associated with increased viral prevalence, while greater floral density was associated with reduced viral prevalence.

"Areas with greater floral abundance could provide better pollen and nectar resources for bees to help them resist or fight off infection," said study co-author Elizabeth Tibbetts, a professor in the U-M Department of Ecology and Evolutionary Biology who was Fearon's dissertation adviser. "Additionally, greater floral abundance may reduce the effective foraging density of pollinators and result in reduced pathogen transmission."

More natural area was also associated with higher bee species diversity, which in turn contributed to reduced, or diluted, viral prevalence.

"Most importantly, we found that greater habitat quality in the surrounding landscape was a key driver of the dilution effect that we previously observed," Fearon said. "This provides evidence for a habitat-driven biodiversity-disease relationship, where habitat quality indirectly impacts bee health by altering bee species diversity.

"But different habitat-quality metrics impacted patterns of viral prevalence both positively and negatively. This means that habitat quality has the potential to decrease or increase viral prevalence in pollinators depending on the relative strengths of the habitat-disease and biodiversity-disease pathways.

"So, it is important to consider how improving specific habitat quality measures may impact bee diversity and bee health in different ways."

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Parkinson's medication improved blood pressure in teens with Type 1 diabetes

Teens with Type 1 diabetes (T1D) who took bromocriptine, a medication used to treat Parkinson's disease and Type 2 diabetes, had lower blood pressure and less stiff arteries after one month of treatment compared to those who did not take the medicine, according to a small study published today in Hypertension, an American Heart Association journal.

High blood pressure and stiff arteries contribute to the development of heart disease. People with T1D, a lifelong, chronic condition in which the pancreas doesn't produce enough insulin to control blood sugar levels, have a higher risk of developing heart disease than those without the condition. Those diagnosed with T1D as children have even higher risks for heart disease than people diagnosed in adulthood. Therefore, researchers are interested in ways to slow down the onset of vascular disease in children with T1D.

"We know that abnormalities in the large vessels around the heart, the aorta and its primary branches, begin to develop in early childhood in people with Type 1 diabetes," said lead study author Michal Schäfer, Ph.D., a researcher and fourth-year medical student at the University of Colorado School of Medicine in Aurora, Colorado. "We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population."

The multidisciplinary team conducted this study to examine the impact of bromocriptine on blood pressure and aortic stiffness compared with a placebo in adolescents with Type 1 diabetes. Bromocriptine is in a class of medications called dopamine receptor agonists. It increases levels of dopamine, a chemical in the brain, which leads to an increase in the body's responsiveness to insulin, called insulin sensitivity. Bromocriptine has been FDA-approved since 2009 to treat adults with Type 2 diabetes due to its effect on insulin sensitivity.

The study included 34 participants (13 male, 21 female) ages 12 to 21 years who had been diagnosed with Type 1 diabetes for at least a year, and their HbA1c (glycosylated hemoglobin -- a measure of blood glucose) was 12% or less. An HbA1c level of 6.5% or higher indicates diabetes. They were randomly divided into two groups of 17, with one group receiving bromocriptine quick-release therapy and the other receiving a placebo once daily. The study was conducted in two phases. Participants took the first treatment or placebo for 4 weeks in phase 1, then had no treatment for a 4-week "wash-out" period, followed by phase 2 with 4 weeks on the opposite treatment. In this "crossover" design, each participant served as their own control for comparison.

Blood pressure and aortic stiffness were measured at the start of the study and at the end of each phase. Aortic stiffness was determined by assessing the large arteries with cardiovascular magnetic resonance imaging (MRI) and a measurement of the velocity of the blood pressure pulse called pulse wave velocity.

The study found:
 

• Compared to placebo, blood pressure was significantly decreased with bromocriptine. On average, bromocriptine therapy resulted in a systolic blood pressure decrease of 5 mm Hg and a diastolic blood pressure decrease of 2 mm Hg at the end of 4 weeks of treatment.
• Aortic stiffness was also reduced with bromocriptine therapy. The improvement in aortic stiffness was most pronounced in the ascending aorta with a lowered pulse wave velocity of about 0.4 meters/second, and an increase in distensibility, or elasticity, of 8%. In the thoraco-abdominal aorta, bromocriptine was associated with a lowered pulse wave velocity of about 0.2 meters/second, with a 5% increase in distensibility.

"A stiff aorta predisposes a patient to other health issues, such as organ dysfunction or atherosclerosis and higher stress or strain on cardiac muscle," Schäfer said. "We were able to take it a notch further and show, using more sophisticated metrics, that these central large arteries are impaired, and impairment among adolescents and young adults with Type 1 diabetes may be decelerated with this drug."

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Feline genetics help pinpoint first-ever domestication of cats

Nearly 10,000 years ago, humans settling in the Fertile Crescent, the areas of the Middle East surrounding the Tigris and Euphrates rivers, made the first switch from hunter-gatherers to farmers. They developed close bonds with the rodent-eating cats that conveniently served as ancient pest-control in society's first civilizations.

A new study at the University of Missouri found this lifestyle transition for humans was the catalyst that sparked the world's first domestication of cats, and as humans began to travel the world, they brought their new feline friends along with them.

Leslie A. Lyons, a feline geneticist and Gilbreath-McLorn endowed professor of comparative medicine in the MU College of Veterinary Medicine, collected and analyzed DNA from cats in and around the Fertile Crescent area, as well as throughout Europe, Asia and Africa, comparing nearly 200 different genetic markers.

"One of the DNA main markers we studied were microsatellites, which mutate very quickly and give us clues about recent cat populations and breed developments over the past few hundred years," Lyons said. "Another key DNA marker we examined were single nucleotide polymorphisms, which are single-based changes all throughout the genome that give us clues about their ancient history several thousands of years ago. By studying and comparing both markers, we can start to piece together the evolutionary story of cats."

Lyons added that while horses and cattle have seen various domestication events caused by humans in different parts of the world at various times, her analysis of feline genetics in the study strongly supports the theory that cats were likely first domesticated only in the Fertile Crescent before migrating with humans all over the world. After feline genes are passed down to kittens throughout generations, the genetic makeup of cats in western Europe, for example, is now far different from cats in southeast Asia, a process known as 'isolation by distance.'

"We can actually refer to cats as semi-domesticated, because if we turned them loose into the wild, they would likely still hunt vermin and be able to survive and mate on their own due to their natural behaviors," Lyons said. "Unlike dogs and other domesticated animals, we haven't really changed the behaviors of cats that much during the domestication process, so cats once again prove to be a special animal."

Lyons, who has researched feline genetics for more than 30 years, said studies like this also support her broader research goal of using cats as a biomedical model to study genetic diseases that impact both cats and people, such as polycystic kidney disease, blindness and dwarfism.

"Comparative genetics and precision medicine play key roles in the 'One Health' concept, which means anything we can do to study the causes of genetic diseases in cats or how to treat their ailments can be useful for one day treating humans with the same diseases," Lyons said. "I am building genetic tools, genetic resources that ultimately help improve cat health. When building these tools, it is important to get a representative sample and understand the genetic diversity of cats worldwide so that our genetic toolbox can be useful to help cats all over the globe, not just in one specific region."

Throughout her career, Lyons has worked with cat breeders and research collaborators to develop comprehensive feline DNA databases that the scientific community can benefit from, including cat genome sequencing from felines all around the world. In a 2021 study, Lyons and colleagues found that the cat's genomic structure is more similar to humans than nearly any other non-primate mammal.

"Our efforts have helped stop the migration and passing-down of inherited genetic diseases around the world, and one example is polycystic kidney disease, as 38% of Persian cats had this disease when we first launched our genetic test for it back in 2004," Lyons said. "Now that percentage has gone down significantly thanks to our efforts, and our overall goal is to eradicate genetic diseases from cats down the road."

Currently, the only viable treatment for polycystic kidney disease has unhealthy side effects, including liver failure. Lyons is currently working with researchers at the University of California at Santa Barbara to develop a diet-based treatment trial for those suffering from the disease.

"If those trials are successful, we might be able to have humans try it as a more natural, healthier alternative to taking a drug that may cause liver failure or other health issues," Lyons said. "Our efforts will continue to help, and it feels good to be a part of it."

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Researchers say space atomic clocks could help uncover the nature of dark matter

Studying an atomic clock on-board a spacecraft inside the orbit of Mercury and very near to the Sun might be the trick to uncovering the nature of dark matter, suggests a new study published in Nature Astronomy.

Dark matter makes up more than 80 per cent of mass in the universe, but it has so far evaded detection on Earth, despite decades of experimental efforts. A key component of these searches is an assumption about the local density of dark matter, which determines the number of dark matter particles passing through the detector at any given time, and therefore the experimental sensitivity. In some models, this density can be much higher than is usually assumed, and dark matter can become more concentrated in some regions compared to others.

One important class of experimental searches are those using atoms or nuclei, because these have achieved incredible sensitivity to signals of dark matter. This is possible, in part, because when dark matter particles have very small masses, they induce oscillations in the very constants of nature. These oscillations, for example in the mass of the electron or the interaction strength of the electromagnetic force, modify the transition energies of atoms and nucleii in predictable ways.

An international team of researchers, Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU) Project Researcher Joshua Eby, University of California, Irvine, Postdoctoral Fellow Yu-Dai Tsai, and University of Delaware Professor Marianna S. Safronova, saw potential in these oscillating signals. They claimed that in a particular region of the Solar System, between the orbit of Mercury and the Sun, the density of dark matter may be exceedingly large, which would mean exceptional sensitivity to the oscillating signals.

These signals could be picked up by atomic clocks, which operate by carefully measuring the frequency of photons emitted in transitions of different states in atoms. Ultralight dark matter in the vicinity of the clock experiment could modify those frequencies, as the oscillations of the dark matter slightly increase and decrease the photon energy.

"The more dark matter there is around the experiment, the larger these oscillations are, so the local density of dark matter matters a lot when analyzing the signal," said Eby.

While the precise density of the dark matter near the Sun is not well-known, the researchers argue that even a relatively low-sensitivity search could provide important information.

The density of dark matter is only constrained in the Solar System by information about planet orbits. In the region between the Sun and Mercury, the planet nearest to the Sun, there is almost no constraint. So a measurement onboard a spacecraft could quickly uncover world-leading limits on dark matter in these models.

The technology to put their theory to the test already exists. Eby says the NASA Parker Solar Probe, which has been operating since 2018 with the help of shielding, has travelled closer to the Sun than any human-made craft in history, and is currently operating inside the orbit of Mercury, with plans to move even closer to the Sun within a year.

Atomic clocks in space are already well-motivated for many reasons other than searching for dark matter.

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Playing the piano boosts brain processing power and helps lift the blues

A new study published by researchers at the University of Bath demonstrates the positive impact learning to play a musical instrument has on the brain's ability to process sights and sounds, and shows how it can also help to lift a blue mood.

Publishing their findings in the academic journal Nature Scientific Reports, the team behind the study shows how beginners who undertook piano lessons for just one hour a week over 11 weeks reported significant improvements in recognising audio-visual changes in the environment and reported less depression, stress and anxiety.

In the randomised control study, 31 adults were assigned into either a music training, music listening, or a control group. Individuals with no prior musical experiences or training were instructed to complete weekly one-hour sessions. Whilst the intervention groups played music, the control groups either listened to music or used the time to complete homework.

The researchers found that within just a few weeks of starting lessons*, people's ability to process multisensory information -- i.e., sight and sound -- was enhanced. Improved 'multisensory process' has benefits for almost every activity we participate in -- from driving a car and crossing a road, to finding someone in a crowd or watching TV.

These multisensory improvements extended beyond musical abilities. With musical training, people's audio-visual processing became more accurate across other tasks. Those who received piano lessons showed greater accuracy in tests where participants were asked to determine whether sound and vision 'events' occurred at the same time.

This was true both for simple displays presenting flashes and beeps, and for more complex displays showing a person talking. Such fine-tuning of individuals' cognitive abilities was not present for the music listening group (where participants listened to the same music as played by the music group), or for the non-music group (where members studied or read).

In addition, the findings went beyond improvements in cognitive abilities, showing that participants also had reduced depression, anxiety and stress scores after the training compared to before it. The authors suggest that music training could be beneficial for people with mental health difficulties, and further research is currently underway to test this.

Cognitive psychologist and music specialist Dr Karin Petrini from the University of Bath's Department of Psychology, explained: "We know that playing and listening to music often brings joy to our lives, but with this study we were interested in learning more about the direct effects a short period of music learning can have on our cognitive abilities.

"Learning to play an instrument like the piano is a complex task: it requires a musician to read a score, generate movements and monitor the auditory and tactile feedback to adjust their further actions. In scientific terms, the process couples visual with auditory cues and results in a multisensory training for individuals.

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Fossil discovery in storeroom cupboard shifts origin of modern lizard back 35 million years

A specimen retrieved from a cupboard of the Natural History Museum in London has shown that modern lizards originated in the Late Triassic and not the Middle Jurassic as previously thought.

This fossilised relative of living lizards such as monitor lizards, gila monsters and slow worms was identified in a stored museum collection from the 1950s, including specimens from a quarry near Tortworth in Gloucestershire, South West England. The technology didn't exist then to expose its contemporary features.

As a modern-type lizard, the new fossil impacts all estimates of the origin of lizards and snakes, together called the Squamata, and affects assumptions about their rates of evolution, and even the key trigger for the origin of the group.

The team, led by Dr David Whiteside of Bristol's School of Earth Sciences, have named their incredible discovery Cryptovaranoides microlanius meaning 'small butcher' in tribute to its jaws that were filled with sharp-edged slicing teeth.

Dr Whiteside explained: "I first spotted the specimen in a cupboard full of Clevosaurus fossils in the storerooms of the Natural History Museum in London where I am a Scientific Associate. This was a common enough fossil reptile, a close relative of the New Zealand Tuatara that is the only survivor of the group, the Rhynchocephalia, that split from the squamates over 240 million years ago.

"Our specimen was simply labelled 'Clevosaurus and one other reptile.' As we continued to investigate the specimen, we became more and more convinced that it was actually more closely related to modern day lizards than the Tuatara group.

"We made X-ray scans of the fossils at the University, and this enabled us to reconstruct the fossil in three dimensions, and to see all the tiny bones that were hidden inside the rock."

Cryptovaranoides is clearly a squamate as it differs from the Rhynchocephalia in the braincase, in the neck vertebrae, in the shoulder region, in the presence of a median upper tooth in the front of the mouth, the way the teeth are set on a shelf in the jaws (rather than fused to the crest of the jaws) and in the skull architecture such as the lack of a lower temporal bar. There is only one major primitive feature not found in modern squamates, an opening on one side of the end of the upper arm bone, the humerus, where an artery and nerve pass through. Cryptovaranoides does have some other, apparently primitive characters such as a few rows of teeth on the bones of the roof of the mouth, but experts have observed the same in the living European Glass lizard and many snakes such as Boas and Pythons have multiple rows of large teeth in the same area. Despite this, it is advanced like most living lizards in its braincase and the bone connections in the skull suggest that it was flexible.

"In terms of significance, our fossil shifts the origin and diversification of squamates back from the Middle Jurassic to the Late Triassic," says co-author Professor Mike Benton. "This was a time of major restructuring of ecosystems on land, with origins of new plant groups, especially modern-type conifers, as well as new kinds of insects, and some of the first of modern groups such as turtles, crocodilians, dinosaurs, and mammals.

"Adding the oldest modern squamates then completes the picture. It seems these new plants and animals came on the scene as part of a major rebuilding of life on Earth after the end-Permian mass extinction 252 million years ago, and especially the Carnian Pluvial Episode, 232 million years ago when climates fluctuated between wet and dry and caused great perturbation to life."

PhD research student Sofia Chambi-Trowell commented: "The name of the new animal, Cryptovaranoides microlanius, reflects the hidden nature of the beast in a drawer but also in its likely lifestyle, living in cracks in the limestone on small islands that existed around Bristol at the time. The species name, meaning 'small butcher,' refers to its jaws that were filled with sharp-edged slicing teeth and it would have preyed on arthropods and small vertebrates."

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The future of replacement organs is (quite possibly) here: Robust human intestinal organoids created in a lab

Researchers from Tokyo Medical and Dental University (TMDU) find that spheroids grown in suspension mature into human intestinal organoids when transferred to a bioreactor and differentiate into complex intestinal tissue upon transplantation.

Growing human body parts in the lab is a common trope of horror movies and sci-fi books. But growing miniature organ-like tissues in the lab is already within our reach. Researchers from Japan have developed a new approach that enables intestinal mini-organs to be grown more easily and efficiently in the lab. This holds immense promise for regenerative medicine.

In a study published in November in Cell Reports Methods, researchers from Tokyo Medical and Dental University (TMDU) reveal that applying a few specialized lab techniques yields intestine-like tissues of predictable size and composition.

Organoids are organ-like balls of cells that are grown in the lab from spheroids (even smaller balls) of human cells and mimic the properties of the organ from which the "seed" cell was taken. Organoids are used for studying organ function in a lab setting and are also promising tools in the field of regenerative medicine.

"There are established methods for growing human intestinal organoids (HIOs) from induced pluripotent stem cells (iPSCs)," states Junichi Takahashi, first author of the study. "However, these techniques are challenging to perform. They result in spheroids of varying sizes and are limited by the growth conditions, which can result in deformed and unhealthy spheroids over time."

To develop a more robust and consistent way to generate HIOs, the researchers explored the use of cell culture plates made with an ultra-low attachment polymer to encourage the cells to detach and grow in suspension. They also tested the effects of growing the resulting spheroids in a bioreactor, a specialized incubator that keeps the growth medium constantly flowing to improve the health of the cells.

"Using our technique, we were able to grow spheroids of a predictable, consistent size that could be modified by modulating the number of cells seeded into the plates," says Tomohiro Mizutani, corresponding author of the study. "Furthermore, transferring the spheroids to a bioreactor allowed them to grow even larger, into healthy HIOs."

These organoids were surrounded by mesenchyme, which is a type of tissue found between organs in the human body. Importantly, when the organoids were transplanted into mice, they continued to grow and differentiate, developing a complex tissue architecture reflecting that of mature intestine. "Our findings show that intestinal tissue can be generated from iPSC-derived HIOs by inducing spheroids in suspension and maturing them in a bioreactor," says Takahashi.

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Rare sighting of luminous jet spewed by supermassive black hole

What happens when a dying star flies too close to a supermassive black hole?

According to University of Maryland astronomer Igor Andreoni, several things happen: first, the star is violently ripped apart by the black hole's gravitational tidal forces -- similar to how the Moon pulls tides on Earth but with greater strength. Then, pieces of the star are captured into a swiftly spinning disk orbiting the black hole. Finally, the black hole consumes what remains of the doomed star in the disk. This is what astronomers call a tidal disruption event (TDE).

But in some extremely rare cases, the supermassive black hole launches "relativistic jets" -- beams of matter traveling close to the speed of light -- after destroying a star. Andreoni, who is a postdoctoral associate in the Department of Astronomy at UMD and NASA Goddard Space Flight Center, discovered one such case with his team in the Zwicky Transient Facility (ZTF) survey in February 2022. After the group publicly announced the sighting, the event was named "AT2022cmc." The team published its findings in the journal Nature on November 30, 2022.

"The last time scientists discovered one of these jets was well over a decade ago," said Michael Coughlin, an assistant professor of astronomy at the University of Minnesota Twin Cities and co-lead on the project. "From the data we have, we can estimate that relativistic jets are launched in only 1% of these destructive events, making AT2022cmc an extremely rare occurrence. In fact, the luminous flash from the event is among the brightest ever observed."

Before AT2022cmc, the only two previously known jetted TDEs were discovered through gamma-ray space missions, which detect the highest-energy forms of radiation produced by these jets. As the last such discovery was made in 2012, new methods were required to find more events of this nature. To help address that need, Andreoni and his team implemented a novel, "big picture" tactic to find AT2022cmc: ground-based optical surveys, or general maps of the sky without specific observational targets. Using ZTF, a wide-field sky survey taken by the Samuel Oschin Telescope in California, the team was able to identify and uniquely study the otherwise dormant-looking black hole.

"We developed an open-source data pipeline to store and mine important information from the ZTF survey and alert us about atypical events in real time," Andreoni explained. "The rapid analysis of ZTF data, the equivalent to a million pages of information every night, allowed us to quickly identify the TDE with relativistic jets and make follow-up observations that revealed an exceptionally high luminosity across the electromagnetic spectrum, from the X-rays to the millimeter and radio."

Follow up observations with many observatories confirmed that AT2022cmc was fading rapidly and the ESO Very Large Telescope revealed that AT2022cmc was at cosmological distance, 8.5 billion light years away.

Hubble Space Telescope optical/infrared images and radio observations from the Very Large Array pinpointed the location of AT2022cmc with extreme precision. The researchers believe that AT2022cmc was at the center of a galaxy that is not yet visible because the light from AT2022cmc outshone it, but future space observations with Hubble or James Webb Space Telescopes may unveil the galaxy when the transient eventually disappears.

It is still a mystery why some TDEs launch jets while others do not seem to. From their observations, Andreoni and his team concluded that the black holes in AT2022cmc and other similarly jetted TDEs are likely spinning rapidly so as to power the extremely luminous jets. This suggests that a rapid black hole spin may be one necessary ingredient for jet launching -- an idea that brings researchers closer to understanding the physics of supermassive black holes at the center of galaxies billions of light years away.

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Scientists reveal encouraging findings in first-in-human clinical trial evaluating HIV vaccine approach

While scientists have struggled in the past to create an effective vaccine against HIV, a novel vaccine design strategy being pursued by researchers at Scripps Research, IAVI, Fred Hutchinson Cancer Center (Fred Hutch) and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) shows new promise, according to data from a first-in-human clinical trial.

In a paper published in Science on December 2, 2022, the scientists reveal critical new insights into their novel vaccine strategy, which involves a stepwise approach to producing antibodies capable of targeting a wide range of HIV variants.

"The data we are publishing in Science demonstrates for the first time that one can design a vaccine that elicits made-to-order antibodies in humans. We specified in advance certain molecular properties of the antibodies that we wanted to elicit, and the results of this trial show that our vaccine antigen consistently induced precisely those types of antibodies," says co-senior author William Schief, PhD, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI's Neutralizing Antibody Center, whose laboratory developed the vaccine antigen. "We believe this vaccine design strategy will be essential to make an HIV vaccine and may help the field create vaccines for other difficult pathogens."

The Phase 1 trial, known as IAVI G001, tested the first stage in a multi-stage HIV vaccine regimen the researchers are developing. The trial results show that the vaccine had a favorable safety profile and induced the targeted response in 97% of people who were vaccinated. Importantly, the Science study also provides a detailed immunological analysis of the vaccine responses.

"HIV represents an area of dire unmet need across the world, which is what makes the findings from our Phase 1 clinical trial so encouraging," says Mark Feinberg, MD, PhD, president and CEO of IAVI. "Through the close-knit collaboration of many different scientists, disciplines and institutions, we are that much closer to designing an effective vaccine that could help end the HIV pandemic."

Priming the Immune System

Broadly neutralizing antibodies (bnAbs) are a rare type of antibody that can fight and protect against many different variants of a virus -- including HIV. This is why scientists have tried to develop an HIV vaccine that induces bnAbs, but thus far without success.

The researchers in the study are using a strategy known as 'germline targeting' to eventually produce bnAbs that can protect against HIV. The first step of germline targeting involves stimulating the rare immune cells -- known as bnAb-precursor B cells -- that can eventually evolve into the cells that produce the bnAbs needed to block the virus. To accomplish this first step, the researchers designed a customized molecule -- known as an immunogen -- that would "prime" the immune system and elicit responses from these rare bnAb-precursor cells.

The overarching goal of the IAVI G001 trial was to determine if the vaccine had an acceptable safety profile and could induce responses from these bnAb-precursor B cells.

"Through extensive safety and tolerability monitoring during the trial, we showed the vaccine had a favorable safety profile, while still inducing the necessary target cells," says study author Dagna Laufer, MD, vice president and head of clinical development at IAVI. "This represents a large step forward in developing an HIV vaccine that is both safe and effective."

To determine if the targeted bnAb-precursor B cells were induced, the researchers carried out a sophisticated analytical process.

"The workflow of multidimensional immunological analyses has taken clinical trial evaluation to the next level," says co-senior author Adrian B. McDermott, PhD, former chief of the Vaccine Immunology Program at the NIAID VRC. "In evaluating these important immunological factors, we helped show why the vaccine antigen was able to induce the targeted response in 97% of vaccine recipients."

IAVI G001 was sponsored by IAVI and took place at two sites: George Washington University (GWU) in Washington, D.C., and Fred Hutch in Seattle, enrolling 48 healthy adult volunteers. Participants received either a placebo or two doses of the vaccine antigen, eOD-GT8 60mer, along with an adjuvant developed by the pharmaceutical company GSK. Julie McElrath, MD, PhD, co-senior author, senior vice president and director of Fred Hutch's Vaccine and Infectious Disease Division, and David Diemert, MD, professor of medicine at GWU School of Medicine and Health Sciences, were lead investigators at the trial sites.

A Deeper Immunological Dive

The study also carefully examined the properties of the antibodies and B cells induced by the vaccine antigen, in what Schief likens to "looking under the car hood" to understand how the immune system operated in response to the vaccine. One analysis showed that the vaccine antigen first stimulated an average of 30 to 65 different bnAb precursors per person vaccinated, and then caused those cells to multiply. This helped explain why the vaccine induced the desired response in almost all participants.

Other analyses delved into the specific mutations the bnAb-precursor B cells acquired over time and how tightly they bound to the vaccine antigen. These investigations showed that that after each dose of the vaccine, the bnAb-precursor B cells gained affinity and continued along favorable maturation pathways.

One concern for this type of vaccine approach is the notion of "competitors" -- in other words, the B cells induced by the vaccine antigen that are not bnAb precursors. The researchers extensively studied the "competitor" responses, and the results were very encouraging. Although the majority of the B cells triggered by vaccination were, in fact, "competitors," these undesired B cells could not match the binding strength of the desired bnAb precursors and did not seem to impede maturation of the bnAb-precursor responses.

"These findings were very encouraging, as they indicated that immunogen design principles we used could be applied to many different epitopes, whether for HIV or even other pathogens," adds Schief.

With these promising data in hand spanning both safety and immune responses, the researchers will continue to iterate and design boosting immunogens that could eventually induce the desired bnAbs and provide protection against the virus. These findings also come shortly after two additionalstudies in Immunity published in September 2022, which helped validate the germline-targeting approach for vaccinating against HIV.

"Working together with IAVI, Scripps Research, the VRC, GWU, additional investigators at Fred Hutch and many others, this trial and additional analyses will help inform design of the remaining stages of a candidate HIV vaccine regimen -- while also enabling others in the field to develop vaccine strategies for additional viruses," says McElrath of Fred Hutch.

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Physicists observe wormhole dynamics using a quantum computer

 

Abstract concept illustration, digital worm hole

Scientists have, for the first time, developed a quantum experiment that allows them to study the dynamics, or behavior, of a special kind of theoretical wormhole. The experiment has not created an actual wormhole (a rupture in space and time), rather it allows researchers to probe connections between theoretical wormholes and quantum physics, a prediction of so-called quantum gravity. Quantum gravity refers to a set of theories that seek to connect gravity with quantum physics, two fundamental and well-studied descriptions of nature that appear inherently incompatible with each other.

"We found a quantum system that exhibits key properties of a gravitational wormhole yet is sufficiently small to implement on today's quantum hardware," says Maria Spiropulu, the principal investigator of the U.S. Department of Energy Office of Science research program Quantum Communication Channels for Fundamental Physics (QCCFP) and the Shang-Yi Ch'en Professor of Physics at Caltech. "This work constitutes a step toward a larger program of testing quantum gravity physics using a quantum computer. It does not substitute for direct probes of quantum gravity in the same way as other planned experiments that might probe quantum gravity effects in the future using quantum sensing, but it does offer a powerful testbed to exercise ideas of quantum gravity."

The research will be published December 1 in the journal Nature. The study's first authors are Daniel Jafferis of Harvard University and Alexander Zlokapa (BS '21), a former undergraduate student at Caltech who started on this project for his bachelor's thesis with Spiropulu and has since moved on to graduate school at MIT.

Wormholes are bridges between two remote regions in spacetime. They have not been observed experimentally, but scientists have theorized about their existence and properties for close to 100 years. In 1935, Albert Einstein and Nathan Rosen described wormholes as tunnels through the fabric of spacetime in accordance with Einstein's general theory of relativity, which describes gravity as a curvature of spacetime. Researchers call wormholes Einstein-Rosen bridges after the two physicists who invoked them, while the term "wormhole" itself was coined by physicist John Wheeler in the 1950s.

The notion that wormholes and quantum physics, specifically entanglement (a phenomenon in which two particles can remain connected across vast distances), may have a connection was first proposed in theoretical research by Juan Maldacena and Leonard Susskind in 2013. The physicists speculated that wormholes (or "ER") were equivalent to entanglement (also known as "EPR" after Albert Einstein, Boris Podolsky [PhD '28], and Nathan Rosen, who first proposed the concept). In essence, this work established a new kind of theoretical link between the worlds of gravity and quantum physics. "It was a very daring and poetic idea," says Spiropulu of the ER = EPR work.

Later, in 2017, Jafferis, along with his colleagues Ping Gao and Aron Wall, extended the ER = EPR idea to not just wormholes but traversable wormholes. The scientists concocted a scenario in which negative repulsive energy holds a wormhole open long enough for something to pass through from one end to the other. The researchers showed that this gravitational description of a traversable wormhole is equivalent to a process known as quantum teleportation. In quantum teleportation, a protocol that has been experimentally demonstrated over long distances via optical fiber and over the air, information is transported across space using the principles of quantum entanglement.

The present work explores the equivalence of wormholes with quantum teleportation. The Caltech-led team performed the first experiments that probe the idea that information traveling from one point in space to another can be described in either the language of gravity (the wormholes) or the language of quantum physics (quantum entanglement).

A key finding that inspired possible experiments occurred in 2015, when Caltech's Alexei Kitaev, the Ronald and Maxine Linde Professor of Theoretical Physics and Mathematics, showed that a simple quantum system could exhibit the same duality later described by Gao, Jafferis, and Wall, such that the model's quantum dynamics are equivalent to quantum gravity effects. This Sachdev-Ye-Kitaev, or SYK model (named after Kitaev, and Subir Sachdev and Jinwu Ye, two other researchers who worked on its development previously) led researchers to suggest that some theoretical wormhole ideas could be studied more deeply by doing experiments on quantum processors.

Furthering these ideas, in 2019, Jafferis and Gao showed that by entangling two SYK models, researchers should be able to perform wormhole teleportation and thus produce and measure the dynamical properties expected of traversable wormholes.

In the new study, the team of physicists performed this type of experiment for the first time. They used a "baby" SYK-like model prepared to preserve gravitational properties, and they observed the wormhole dynamics on a quantum device at Google, namely the Sycamore quantum processor. To accomplish this, the team had to first reduce the SYK model to a simplified form, a feat they achieved using machine learning tools on conventional computers.

"We employed learning techniques to find and prepare a simple SYK-like quantum system that could be encoded in the current quantum architectures and that would preserve the gravitational properties," says Spiropulu. "In other words, we simplified the microscopic description of the SYK quantum system and studied the resulting effective model that we found on the quantum processor. It is curious and surprising how the optimization on one characteristic of the model preserved the other metrics! We have plans for more tests to get better insights on the model itself."

In the experiment, the researchers inserted a qubit -- the quantum equivalent of a bit in conventional silicon-based computers -- into one of their SYK-like systems and observed the information emerge from the other system. The information traveled from one quantum system to the other via quantum teleportation -- or, speaking in the complementary language of gravity, the quantum information passed through the traversable wormhole.

"We performed a kind of quantum teleportation equivalent to a traversable wormhole in the gravity picture. To do this, we had to simplify the quantum system to the smallest example that preserves gravitational characteristics so we could implement it on the Sycamore quantum processor at Google," says Zlokapa.

Co-author Samantha Davis, a graduate student at Caltech, adds, "It took a really long time to arrive at the results, and we surprised ourselves with the outcome."

"The near-term significance of this type of experiment is that the gravitational perspective provides a simple way to understand an otherwise mysterious many-particle quantum phenomenon," says John Preskill, the Richard P. Feynman Professor of Theoretical Physics at Caltech and director of the Institute for Quantum Information and Matter (IQIM). "What I found interesting about this new Google experiment is that, via machine learning, they were able to make the system simple enough to simulate on an existing quantum machine while retaining a reasonable caricature of what the gravitation picture predicts."

In the study, the physicists report wormhole behavior expected both from the perspectives of gravity and from quantum physics. For example, while quantum information can be transmitted across the device, or teleported, in a variety of ways, the experimental process was shown to be equivalent, at least in some ways, to what might happen if information traveled through a wormhole. To do this, the team attempted to "prop open the wormhole" using pulses of either negative repulsive energy pulse or the opposite, positive energy. They observed key signatures of a traversable wormhole only when the equivalent of negative energy was applied, which is consistent with how wormholes are expected to behave.

"The high fidelity of the quantum processor we used was essential," says Spiropulu. "If the error rates were higher by 50 percent, the signal would have been entirely obscured. If they were half we would have 10 times the signal!"?

In the future, the researchers hope to extend this work to more complex quantum circuits. Though bona fide quantum computers may still be years away, the team plans to continue to perform experiments of this nature on existing quantum computing platforms.

"The relationship between quantum entanglement, spacetime, and quantum gravity is one of the most important questions in fundamental physics and an active area of theoretical research," says Spiropulu. "We are excited to take this small step toward testing these ideas on quantum hardware and will keep going."

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