When stressed out, many of us turn to junk food for solace. But new University of Colorado Boulder research suggests this strategy may backfire.
The study found that in animals, a high-fat diet disrupts resident gut bacteria, alters behavior and, through a complex pathway connecting the gut to the brain, influences brain chemicals in ways that fuel anxiety.
“Everyone knows that these are not healthy foods, but we tend to think about them strictly in terms of a little weight gain,” said lead author Christopher Lowry, a professor of integrative physiology at CU Boulder. “If you understand that they also impact your brain in a way that can promote anxiety, that makes the stakes even higher.”
Lowry’s team divided adolescent rats into two groups: Half got a standard diet of about 11% fat for nine weeks; the others got a high-fat diet of 45% fat, consisting mostly of saturated fat from animal products.
The typical American diet is about 36% fat, according to the Centers for Disease Control and Prevention.
Throughout the study, the researchers collected fecal samples and assessed the animals’ microbiome, or gut bacteria. After nine weeks, the animals underwent behavioral tests.
When compared to the control group, the group eating a high-fat diet, not surprisingly, gained weight. But the animals also showed significantly less diversity of gut bacteria. Generally speaking, more bacterial diversity is associated with better health, Lowry explained. They also hosted far more of a category of bacteria called Firmicutes and less of a category called Bacteroidetes. A higher Firmicutes to Bacteroidetes ratio has been associated with the typical industrialized diet and with obesity.

The high-fat diet group also showed higher expression of three genes (tph2, htr1a, and slc6a4) involved in production and signaling of the neurotransmitter serotonin — particularly in a region of the brainstem known as the dorsal raphe nucleus cDRD, which is associated with stress and anxiety.
While serotonin is often billed as a “feel-good brain chemical,” Lowry notes that certain subsets of serotonin neurons can, when activated, prompt anxiety-like responses in animals. Notably, heightened expression of tph2, or tryptophan hydroxylase, in the cDRD has been associated with mood disorders and suicide risk in humans.
“To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary,” said Lowry. “The high-fat group essentially had the molecular signature of a high anxiety state in their brain.”
Lowry suspects that an unhealthy microbiome compromises the gut lining, enabling bacteria to slip into the body’s circulation and communicate with the brain via the vagus nerve, a pathway from the gastrointestinal tract to the brain.
“If you think about human evolution, it makes sense,” Lowry said. “We are hard-wired to really notice things that make us sick so we can avoid those things in the future.”
Lowry stresses that not all fats are bad, and that healthy fats like those found in fish, olive oil, nuts and seeds can be anti-inflammatory and good for the brain.
His advice: Eat as many different kinds of fruits and vegetables as possible, add fermented foods to your diet to support a healthy microbiome and lay off the pizza and fries. Also, if you do have a hamburger, add a slice of avocado. Some research shows that good fat can counteract some of the bad.

Researchers at the Francis Crick Institute, UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital for Children (GOSH) have designed a new genetic therapy that could alleviate debilitating giant moles in a rare skin condition.
In the future, the treatment could potentially be used to reverse the giant moles, and therefore reduce the risk of affected children and adults from developing cancer. It could also potentially reverse other more common types of at-risk moles as an alternative to surgery.
Small skin moles are common in the population, but in congenital melanocytic naevus syndrome (CMN), children are born with up to 80% of their body covered in big, painful or itchy moles, caused by mutations acquired in the womb. These moles can sometimes develop into a severe type of cancer called melanoma.
Published today in the Journal of Investigate Dermatology, the researchers silenced a gene called NRAS, which is mutated in the cells in these moles, in cells in a dish and in mice. NRAS belongs to a group of genes (RAS genes) that, when mutated, can cause moles, and can predispose to cancer.
The team used a genetic therapy called silencing RNA, which silences the mutated NRAS in mole skin cells. The therapy was delivered in special particles directly to mole cells.
They gave injections containing the therapy to mice with CMN, which reduced the silenced the NRAS gene after just 48 hours. They also tested it in cells and whole skin sections from children with CMN. Silencing the gene triggered the mole cells to self-destruct.
Veronica Kinsler, Principal Group Leader of the Mosaicism and Precision Medicine Laboratory at the Crick, Professor of Paediatric Dermatology and Dermatogenetics at GOSH/UCL, and NIHR Research Professor, said: “CMN is physically and mentally challenging for children and adults living with this condition and for their families. These results are very exciting, as not only does the genetic therapy trigger self-destruction of the mole cells in the lab, but we have managed to deliver it into the skin in mice. This results suggest that the treatment in future could potentially reverse moles in people, however more testing will be needed before we can give it to patients.

“We are very grateful to our patients at Great Ormond Street Hospital, who have been actively participating over many years to help us produce this new potential therapy. After more studies, we hope the therapy can soon enter clinical trials in people.”
This research was funded by the National Institute for Health and Care Research (NIHR), Caring Matters Now Charity and Patient Support Group, LifeArc and the NIHR Great Ormond Street Hospital Biomedical Research Centre.
Jodi Whitehouse, CEO of Caring Matters Now, who helped to fund the research, said: “This breakthrough in finding a treatment for CMN could transform the lives of the families we support living with CMN. As someone who was born with CMN covering 70% of my body and having undergone 30+ operations in my childhood to try and remove the CMN because of the fear of melanoma, with no success, this news is awe-inspiring and exciting. It brings real hope to the lives of those living with CMN.”
Catriona Crombie, Head of Rare Disease at LifeArc, said: “This work is part of our commitment to improving the lives of people living with rare diseases, by investing in promising research and helping scientists to overcome translational research barriers. If successful, we hope to see human clinical trials for this therapy within the next few years.”
The researchers have been working closely with the Crick’s Translation team to develop the technology towards patient benefit. This has included securing translational funds from LifeArc, to carry out more research in mice to understand how the treatment works over a longer period.

A new study from Duke-NUS Medical School has highlighted the widespread use of physical restraints among caregivers of older adults with advanced dementia living at home, revealing a need for better guidance and alternative care approaches. Nearly half (47%) of the caregivers surveyed reported physical restraints were used on family members with dementia, pointing to a gap in support and resources.
In Singapore, the ageing population is growing rapidly, with those aged 65 and older expected to comprise nearly a quarter of the population by 2030[1]. Among this demographic, at least 10% are expected to develop dementia[2]. While the use of restraints has been extensively studied and largely prohibited in nursing homes in other countries, this study is the first to examine their prevalence and the factors leading to their use in home settings, where the majority of older adults with dementia in Singapore receive care.
Assistant Professor Chetna Malhotra from the Lien Centre for Palliative Care at Duke-NUS, who supervised the study, said:
“The care of older adults with severe dementia presents unique challenges, especially when physical restraints are involved. These practices, while sometimes used out of a perceived necessity for safety, can impact older adults’ physical and psychological health. It has also been associated with depression, post-traumatic stress, incontinence and increased rate of cognitive decline.”
The study, published in the Journal of the American Geriatrics Society, surveyed 215 family caregivers of patients with advanced dementia. The participants were recruited from public hospitals, home care foundations and hospices between May 2018 and March 2021.
The researchers found that common types of restraints used included belts or sheet ties (56%), locked geriatric chairs with fixed tray tables (35%), hand mittens (31%) and ankle or wrist ties (25%). The most common reasons for using these items were: safety (protection from falls and preventing of wandering), preventing removal of catheters or feeding tubes and managing agitated behaviour.
However, the research team pointed out that feeding tubes have not been shown to improve quality of life or prolong survival for older adults with severe dementia. Instead, clinical guidelines recommend careful hand feeding.

Likewise, agitation is a complex response behaviour that can be particularly taxing for caregivers when accompanied by irritability, restlessness or in rare cases, violence. It also signals unmet needs or a deterioration in health. Caregivers may need help to identify the source of the behaviour and come up with a way to manage it (e.g., reducing noise levels or playing soothing music) that provides compassionate and responsive care while avoiding restraints.
Survey respondents were divided on how physical restraints affected older adults’ quality of life with 39 per cent suggesting it was not affected, 44 per cent indicating reduced, and 17 per cent indicating improved.
The study also found that caregivers who had strong emotional support from friends were less likely to report restraint use. On the other hand, caregivers with higher psychological distress, or who had other caregiving responsibilities, were more likely to report restraint use.
Dr Ellie Bostwick Andres, first author of the paper and a senior research fellow from the Lien Centre for Palliative Care at Duke-NUS, said:
“There is a concern for caregivers under pressure without adequate support. Many caregivers, struggling to balance employment and caregiving, view restraints as a necessary measure for safety. Unfortunately, they might not be fully aware of the detrimental effects these can have on their loved ones.”
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said:
“As Singapore confronts the challenges of an ageing population, understanding the use of restraints in home care is critical. This study not only raises awareness but also calls for a shift towards more supportive approaches to dementia care at home, ensuring better outcomes for older adults and their families.”

Duke-NUS is a leader in medical research and education, with a commitment to improving patient care through innovative scientific discovery. This study is part of its ongoing efforts to enhance palliative care research and education, especially for patients with neurological conditions in our ageing population.
This work was supported by the Singapore Ministry of Health through the National Medical Research Council Office, MOH Holdings Pte Ltd, under its Health Services Research Grant (NMRC/HSRG/0081/2017), and Lien Centre for Palliative Care Research Award.
[1] Population in Brief. 2021
[2] https://www.imh.com.sg/Research/Research-Programmes/Pages/Well-being-of-the-Singapore-Elderly-WiSE.aspx

Research led by Irving Coy Allen in the Virginia-Maryland College of Veterinary Medicine has unlocked a pathway to possible future treatments for colorectal cancer in humans.
A paper published in May in the American Gastroenterological Association journal Cellular and Molecular Gastroenterology and Hepatology focuses on NF-kB-inducing kinase (NIK) and its importance in triggering cellular responses that reduce the risk of the development of colorectal cancer.
“The gene itself is colloquially called NIK, and it encodes a protein that is a kinase, which means it basically turns on or turns off — mostly turns on — lots of different genes and pathways,” said Allen, professor of inflammatory diseases in the Department of Biomedical Sciences and Pathology. “It gives us a central spoke in a hub of biological mechanisms that can be targeted with possible therapeutics. We do know that there are companies working on developing drugs to target NIK. We’re hoping that this can provide them with incentive to go after these drug candidates more aggressively.”
Colorectal cancer is second deadliest form of cancer in the United States, killing over 52,000 people in 2023. Present treatment options are often based on chemotherapy and can be difficult for the patient to endure.
“By identifying new markers and new drug targets, it may provide us with better therapeutic approaches that can minimize side effects and improve overall patient outcomes,” Allen said.
While much of the study was conducted examining mice, and that alone could have generated valuable research, Allen’s team took the extra step of translating it directly to human patients.
“By modeling it in mice, we were able to identify things to look for in humans,” Allen said. “Through collaboration with the Duke University Medical Center and colleagues here at the Virginia Tech Carilion School of Medicine, we were able to get human specimens to confirm that what we were observing in the mouse models was also true in in human colorectal cancer patients.”
The medical application of the findings will be determined in years to come as other researchers seek to identify treatments that can target NIK and its interactions with other proteins.

“Our study identified changes in a significant signaling pathway in human patients,” Allen said. “That presents a variety of possible targets that have not been previously evaluated in that pathway where you could potentially design therapeutics.”
Publication of the paper represents the conclusion of a lengthy study for Allen. Graduate students Kristin Eden ’06, DVM ’10, Ph.D. ’18; Holly Morrison Ph.D. ’23; and Brie Trusiano Ph.D. ’24 took turns helping Allen with the research and carrying it to the finish line.
“When I first came here 12 years ago, my postdoctorate work had identified some hints that this pathway might be important in the context of colorectal cancer and also in the context of inflammatory bowel disease,” Allen said. “Completion of this work has been very satisfying, knowing that it helped to launch the careers of these three talented graduate students and several undergraduate researchers as well.”
Allen said because his studies on the NIK pathway in colorectal cancer are concluded, he and his team will turn toward other types of cancer impacted by NIK and the signaling pathways it controls. But he hopes others can carry the findings forward for life-saving improvements in colorectal cancer treatment.

Could measuring protein clumps in our cells be a new way to find out our risk of getting age-related diseases? Professor Dorothee Dormann and Professor Edward Lemke of Johannes Gutenberg University Mainz (JGU), who are also adjunct directors at the Institute of Molecular Biology (IMB) in Mainz, propose the concept of a “protein aggregation clock” to measure ageing and health in a new perspective article published in Nature Cell Biology.
As we age, the DNA and proteins that make up our bodies gradually undergo changes that cause our bodies to no longer work as well as before. This in turn makes us more prone to getting age-related diseases, such as cardiovascular disease, cancer, and Alzheimer’s disease. One important change is that the proteins in our cells can sometimes become misfolded and clump together to form aggregates, so-called amyloids. Misfolding and aggregation can happen to any protein, but a specific group of proteins known as intrinsically disordered proteins (IDPs) are especially prone to forming amyloids. IDPs make up around 30 percent of the proteins in our cells and they are characterized by having no fixed structure. Instead, they are flexible and dynamic, flopping around like strands of cooked spaghetti.
While the molecular mechanisms are widely debated and an important aspect of basic research, scientists know that aggregates formed from IDPs tend to accumulate in many long-lived cells — such as neurons or muscle cells — as we age. Moreover, they can cause many age-related diseases, particularly neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Thus, having many aggregates in a cell could be an indicator of how unhealthy the cell is or if a person is likely to develop an age-related disease soon. In their recently published article, Dormann and Lemke propose that IDP aggregation could be used as a biological “clock” to measure a person’s health and age.
If developed further into a sensitive diagnostic test, a protein aggregation clock could be extremely useful. Firstly, doctors could use it to help diagnose age-related diseases at very early stages or identify people who are not yet sick but have a higher risk of developing disease as they age. This would allow them to be given preventative treatments before they develop severe disease. Secondly, scientists could use it to assess the effects of new experimental treatments to reduce protein aggregation in order to prevent or delay age-related diseases.
“In practice, we are still far away from a routine diagnostic test, and it is important that we improve our understanding of the fundamental mechanisms leading to IDP aggregation,” said Dormann. “However, we want to stimulate thinking and research in the direction of studying protein aggregates to measure biological ageing processes,” Lemke added. “We are optimistic that in the future we will be able to overcome the current challenges of reading a protein aggregation clock through more research on IDP dynamics and making further technological developments.”
Although there are other “clocks” to measure ageing and health, most of them are based on nucleic acids like DNA. Dormann and Lemke think that a biological clock based on proteins would be a useful complement to these existing clocks, as proteins are among the most abundant molecules in cells and are crucial for all cellular functions. With the help of such a protein aggregation clock, they hope that scientists and doctors will be able to move one step closer towards helping people age healthily and preventing age-related diseases.
With their research, Dorothee Dormann and Edward Lemke contribute to the Center for Healthy Ageing (CHA), a virtual research center launched in 2021. The CHA brings together scientists in basic and clinical research from across Mainz who focus on ageing and age-related diseases. Their findings are to be used to promote healthy ageing and to find treatments that help prevent or cure age-related diseases.

Early diagnosis of hepatocellular carcinoma (HCC) — one of the most fatal malignancies — is crucial to improve patient survival. In a breakthrough study investigators report on the development of a serum fusion-gene machine-learning model. This important screening tool may increase the five-year survival rate of patients with HCC from 20% to 90% because of its improved accuracy in early diagnosis of HCC and monitoring the impact of treatment. The study appears in The American Journal of Pathology, published by Elsevier.
HCC is the most common form of liver cancer and accounts for around 90% of cases. Currently, the most common screening test for the HCC biomarker, serum alpha-fetal protein, is not always accurate, and up to 60% of liver cancers are only diagnosed in advanced stages, resulting in a survival rate of only around 20%.
Lead investigator Jian-Hua Luo, MD, PhD, Department of Pathology, High Throughput Genome Center, and Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, explained: “Early diagnosis of liver cancer helps save lives. However, most liver cancers occur insidiously and without many symptoms. This makes early diagnosis challenging. What we need is a cost-effective, accurate, and convenient test to screen early-stage liver cancer in human populations. We wanted to explore if a machine-learning approach could be used to increase the accuracy of screening for HCC based on the status of the fusion genes.”
In the search for a more effective and efficient diagnostic tool topredict non-HCC and HCC cases, investigators analyzed a panel of nine fusion transcripts in serum samples from 61 patients with HCC and 75 patients with non-HCC conditions using real-time quantitative reverse transcription PCR (RT-PCR). Seven of the nine fusions were frequently detected in HCC patients. The researchers generated machine-learning models based on serum fusion-gene levels to predict HCC in the training cohort, using the leave-one-out cross-validation approach.
A four fusion gene logistic regression model produced an accuracy of 83% to 91% in predicting the occurrence of HCC. When combined with serum alpha-fetal protein, the two-fusion gene plus alpha-fetal protein logistic regression model produced 95% accuracy for all the cohorts. Furthermore, quantification of fusion gene transcripts in the serum samples accurately assessed the impact of the treatment and was able to monitor for the recurrence of the cancer.
Dr. Luo commented, “The fusion gene machine-learning model significantly improves the early detection rate of HCC over the serum alpha-fetal protein alone. It may serve as an important tool in screening for HCC and in monitoring the impact of HCC treatment. This test will find patients who are likely to have HCC.”
Dr. Luo concluded, “Early treatment of liver cancer has a 90% five-year survival rate, while late treatment has only 20%. The alternative to this test is to subject every individual with some risk of liver cancer to imaging analysis every six months, which is very costly and ineffective. In addition, when imaging results are ambiguous, this test will help to differentiate malignant versus benign lesions.”

Brain-computer interfaces or BCIs hold immense potential for individuals with a wide range of neurological conditions, but the road to implementation is long and nuanced for both the invasive and noninvasive versions of the technology. Bin He of Carnegie Mellon University is highly driven to improve noninvasive BCIs, and his lab uses an innovative electroencephalogram (EEG) wearable to push the boundaries of what’s possible. For the first time on record, the group successfully integrated a novel focused ultrasound stimulation to realize bidirectional BCI that both encodes and decodes brain waves using machine learning in a study with 25 human subjects. This work opens up a new avenue to significantly enhance not only the signal quality, but also, overall nonivasive BCI performance by stimulating targeted neural circuits.
Noninvasive BCI is lauded for its merits of being cheap, safe and virtually applicable to everyone, but because signals are recorded over the scalp versus inside the brain, low signal quality presents some limitations. The He group is exploring ways to improve the effectiveness of noninvasive BCIs and over time, has used deep learning approaches to decode what an individual was thinking and then facilitate control of a cursor or robotic arm.
In their latest research, published in Nature Communications, the He group demonstrated that through precision noninvasive neuromodulation using focused ultrasound, the performance of a BCI could be improved for communication.
“This paper reports a breakthrough in noninvasive BCIs by integrating a novel focused ultrasound stimulation to realize bidirectional BCI functionality,” explained Bin He, professor of biomedical engineering at Carnegie Mellon University. “Using a communication prosthetic, 25 human subjects spelled out phrases like “Carnegie Mellon” using a BCI speller. Our findings showed that the addition of focused ultrasound neuromodulation significantly boosted the performance of EEG-based BCI. It also elevated theta neural oscillation that enhanced attention and led to enhanced BCI performance.”
For context, a BCI speller is a 6×6 visual motion aide containing the entire alpabet that is commonly used by nonspeakers to communicate. In He’s study, subjects donned an EEG cap and just by looking at the letters, were able to generate EEG signals to spell the desired words. When a focused ultrasound beam was applied externally to the V5 area (part of the visual cortex) of the brain, the performance of the noninvasive BCI greatly improved among subjects. The neuromodulation-integrated BCI actively altered the engagement of neural circuits to maximize the BCI performance, compared to previous uses, which consisted of pure processing and decoding recorded signals.
“The BRAIN Initiative has supported more than 60 ultrasound projects since its inception. This unique application of noninvasive recording and modulation technologies expands the toolkit, with a potentially scalable impact on assisting people living with communication disabilities,” said Dr. Grace Hwang, program director at the Brain Research Through Advancing Innovative Neurotechnologies® initiative (The BRAIN Initiative®) at the National Institutes of Health (NIH).
Following this discovery, the He lab is further investigating the merits and applications of focused ultrasound neuromodulation to the brain, beyond the visual system, to enhance noninvasive BCIs. They also aim to develop more compact-focused ultrasound neuromodulation device for better integration with EEG-based BCIs, and to integrate AI to continue to enhance the overall system performance.
“This is my lifelong interest, and I will never give up,” emphasized He. “Working to improve noninvasive technology is difficult, but I strongly believe that if we can find a way to make it work, everyone will benefit. I will keep working, and someday, noninvasive lifesaving technology will be available for every household.”

Since the very first instant after the Big Bang the Universe has been expanding. This means that the early Universe was considerably smaller and early-formed galaxies were more likely to interact and merge. Galaxy mergers fuel the formation of quasars — extremely luminous galactic cores where gas and dust falling into a central supermassive black hole emit enormous amounts of light. So when looking back at the early Universe astronomers would expect to find numerous pairs of quasars in close proximity to each other as their host galaxies undergo mergers. However, they have been surprised to find exactly none — until now.
With the aid of the Gemini North telescope, one half of the International Gemini Observatory, which is supported in part by the U.S. National Science Foundation and operated by NSF NOIRLab, a team of astronomers have discovered a pair of merging quasars seen only 900 million years after the Big Bang. Not only is this the most distant pair of merging quasars ever found, but also the first confirmed pair in the period of the Universe’s history known as Cosmic Dawn.
Cosmic Dawn spanned from about 50 million years to one billion years after the Big Bang. During this period the first stars and galaxies began appearing, filling the dark Universe with light for the first time. The arrival of the first stars and galaxies kicked off a new era in the formation of the cosmos known as the Epoch of Reionization.
The Epoch of Reionization, which took place within Cosmic Dawn, was a period of cosmological transition. Beginning roughly 400 million years after the Big Bang, ultraviolet light from the first stars, galaxies and quasars spread throughout the cosmos, interacting with the intergalactic medium and stripping the Universe’s primordial hydrogen atoms of their electrons in a process known as ionization. The Epoch of Reionization was a critical epoch in the history of the Universe that marked the end of the cosmic dark ages and seeded the large structures we observe in our local Universe today.
To understand the exact role that quasars played during the Epoch of Reionization, astronomers are interested in finding and studying quasars populating this early and distant era. “The statistical properties of quasars in the Epoch of Reionization tell us many things, such as the progress and origin of the reionization, the formation of supermassive black holes during Cosmic Dawn, and the earliest evolution of the quasar host galaxies,” said Yoshiki Matsuoka, an astronomer at Ehime University in Japan and lead author of the paper describing these results, published in the Astrophysical Journal Letters.
About 300 quasars have been discovered in the Epoch of Reionization, but none of them have been found in a pair. That is until Matsuoka and their team were reviewing images taken with the Hyper Suprime-Cam on the Subaru Telescope and a faint patch of red caught their eye. “While screening images of quasar candidates I noticed two similarly and extremely red sources next to each other,” said Matsuoka. “The discovery was purely serendipitous.”
The team was not sure that they were a quasar pair since distant quasar candidates are contaminated by numerous other sources, such as foreground stars and galaxies and the effects of gravitational lensing. To confirm the nature of these objects the team conducted follow-up spectroscopy using the Faint Object Camera and Spectrograph (FOCAS) on the Subaru Telescope and the Gemini Near-Infrared Spectrograph (GNIRS) on Gemini North. The spectra, which break down the emitted light from a source into its component wavelengths, obtained with GNIRS were crucial to characterizing the nature of the quasar pair and their host galaxies.

“What we learned from the GNIRS observations was that the quasars are too faint to detect in near-infrared, even with one of the largest telescopes on the ground,” said Matsuoka. This allowed the team to estimate that a portion of the light detected in the optical wavelength range is not coming from the quasars themselves, but from ongoing star formation taking place in their host galaxies. The team also found that the two black holes are whoppers, each being 100 million times the mass of the Sun. This, coupled with the presence of a bridge of gas stretching between the two quasars, suggests that they and their host galaxies are undergoing a major-scale merger [1].
“The existence of merging quasars in the Epoch of Reionization has been anticipated for a long time. It has now been confirmed for the first time,” said Matsuoka [2].
The Epoch of Reionization connects the earliest formation of cosmic structure to the complex Universe that we observe billions of years later. By studying distant objects from this period astronomers gain valuable insight into the process of reionization and the formation of the first objects in the Universe. More discoveries like this may be on the horizon with NSF-DOE Vera C. Rubin Observatory’s decade-long Legacy Survey of Space and Time (LSST), beginning in 2025, which is poised to detect millions of quasars using its deep imaging capabilities.
Notes
[1] A companion paper accepted for publication in AAS Journals presents further analysis of the quasar pair, the gas bridge between them and their host galaxies using observations taken with the Atacama Large Millimeter/submillimeter Array (ALMA).
[2] There have been candidates, but it is difficult to separate them from possibly gravitationally-lensed images of a single quasar. There are also some candidates for being dual active galactic nuclei embedded in individual Epoch of Reionization galaxies, but these have much lower luminosity (black hole activity) than quasars and are two components within a single galaxy, which are qualitatively different from what is described here.

In studies with genetically engineered mice, Johns Hopkins Medicine researchers say they have identified a potentially new biological target involving Aplp1, a cell surface protein that drives the spread of Parkinson’s disease-causing alpha-synuclein.
The findings, published May 31 in Nature Communications, reveal how Aplp1 connects with Lag3, another cell surface receptor, in a key part of a process that helps spread harmful alpha-synuclein proteins to brain cells. Those protein buildups are hallmarks of Parkinson’s disease.
Notably, the researchers say, Lag3 is already the target of a combination cancer drug approved by the U.S. Food and Drug Administration (FDA) that uses antibodies to “teach” the human immune system what to seek and destroy.
“Now that we know how Aplp1 and Lag3 interact, we have a new way of understanding how alpha-synuclein contributes to the disease progression of Parkinson’s disease,” says Xiaobo Mao, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine and a member of the Institute for Cell Engineering. “Our findings also suggest that targeting this interaction with drugs could significantly slow the progression of Parkinson’s disease and other neurodegenerative diseases.”
Mao co-led the research along with Ted Dawson, M.D., Ph.D., Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Institute for Cell Engineering, Valina Dawson, Ph.D. and Hanseok Ko, Ph.D., professors of neurology at the school of medicine and members of the Institute for Cell Engineering.
Long-standing studies have shown that by clumping together and forming protein deposits, misfolded alpha-synuclein proteins journey from brain cell to brain cell, killing those responsible for producing a neurotransmitter called dopamine, and causing Parkinson’s disease to progress through a type of “programmed” cell death that Johns Hopkins researchers have identified. The process, parthanatos (from the Greek word for “death”), leads to impairments in movement, emotional regulation and thinking.
Aplp1’s bond with Lag3 on the cell’s surface enables healthy brain cells to absorb traveling clumps of alpha-synuclein, leading to cell death, the researchers say.

In mouse studies published in 2016 and 2021, Mao and Dawson’s team identified Lag3’s role in binding with alpha-synuclein proteins, causing Parkinson’s disease to spread. However, those studies indicated that another protein was partially responsible for the cell’s absorption of misfolded alpha-synuclein.
“Our work previously demonstrated that Lag3 wasn’t the only cell surface protein that helped neurons absorb alpha-synuclein, so we turned to Aplp1 in our most recent experiments,” says Valina Dawson.
To determine whether Aplp1 indeed contributed to the spread of harmful alpha-synuclein proteins, researchers used a line of genetically engineered mice lacking either Aplp1 or Lag3 or both Aplp1 and Lag3. In mice without Aplp1 and Lag3, cell absorption of the harmful alpha-synuclein protein dropped by 90%. After injecting mice with the Lag3 antibody, they found that this drug also blocks the interaction of Aplp1 and Lag3, meaning healthy brain cells could no longer absorb disease-causing alpha-synuclein clumps.
The researchers say the Lag3 antibody nivolumab/relatlimab, a drug FDA approved in 2022 for cancer treatment, could play a role in preventing cells from absorbing alpha-synuclein.
“The anti-Lag3 antibody was successful in preventing further spread of alpha-synuclein seeds in the mouse models and exhibited better efficacy than Lag3-depletion because of Aplp1’s close association with Lag3,” Ted Dawson says.
This research has potential applications in treating other neurodegenerative conditions that have no cures, Mao says. In Alzheimer’s disease, which is associated with symptoms of memory loss, mood instability and muscle problems, tau proteins become misfolded and clump together in neurons at high levels, worsening the condition. In Alzheimer’s research, Mao says scientists could try to target Lag3 — which also binds with the dementia-related tau protein — with the same antibody.
With the success of using the Lag3 antibody in mice, Ted Dawson says the next steps would be to conduct anti-Lag3 antibody trials in mice with Parkinson’s disease and Alzheimer’s disease. The Johns Hopkins researchers are also looking into how they could prevent unhealthy cells from releasing disease-causing alpha-synuclein in the first place.
Other researchers on this study are Hao Gu, Donghoon Kim, Yasuyoshi Kimura, Ning Wang, Enquan Xu, Ramhari Kumbhar, Xiaotian Ming, Haibo Wang, Chan Chen, Shengnan Zhang, Chunyu Jia, Yuqing Liu, Hetao Bian, Senthilkumar Karuppagounder, Fatih Akkentli, Qi Chen, Longgang Jia, Heehong Hwang, Su Hyun Lee, Xiyu Ke, Michael Chang, Amanda Li, Jun Yang, Cyrus Rastegar, Manjari Sriparna, Preston Ge, Saurav Brahmachari, Sangjune Kim, Shu Zhang, Haiqing Liu, Sin Ho Kweon, Mingyao Ying and Han Seok Ko from Johns Hopkins; Yasushi Shimoda from the Nagaoka University of Technology; Martina Saar and Ulrike Muller from Heidelberg University; Creg Workman and Dario Vignali of the University of Pittsburgh School of Medicine and Cong Liu of the Chinese Academy of Sciences.
This work was supported by grants from the National Institutes of Health (R01NS107318, R01AG073291, R01AG071820, 1135 RF1NS125592, K01AG056841, R21NS125559, R01NS107404, P01AI108545, R01AI144422), the Parkinson’s Foundation, the Maryland Stem Cell Research Foundation, the American Parkinson Disease Association, the Uehara Memorial Foundation, the JPB Foundation, the Adrienne Helis Malvin Medical Research Foundation, and the Parkinson’s Disease Foundation.

A new aging atlas gives scientists an in-depth view of how individual cells and tissues in worms age and how different lifespan-extending strategies might stop the clock.
Aging impacts all the tissues in our body — from our muscles to our skin. Figuring out how individual tissues and cells age could help researchers better understand the aging process and aid in the development of anti-aging treatments.
Due to their short lifespans, simple body plans, and genetic similarity to humans, many researchers study aging in roundworms. To look at aging at the level of tissues and cells, a team of researchers from HHMI’s Janelia Research Campus, Baylor College of Medicine, and Creighton University School of Medicine profiled gene expression in each cell of adult roundworms at different times during the aging process. They also profiled long-lived strains of worms.
The researchers compiled their results into a complete transcriptomic cell atlas of aging in roundworms. The open-access atlas allows scientists to look at what genes are being expressed in all the worm’s cells at the same time and how gene expression changes over time, both for wildtype worms and worms with extended lifespans.
Using the atlas, the researchers developed tissue-specific “aging clocks,” predictive models they used to tease out the unique aging features of different tissues. The researchers used these clocks to better understand the anti-aging mechanisms in long-lived strains of worms.
The researchers also built the first germ cell fate trajectory map that follows how reproductive cells develop over time, enabling the team to discover age-related changes in cell makeup and gene expression in different stages of reproductive cells.
The atlas also allowed the team to get a view of polyadenylation, a key mechanism for gene regulation and protein diversification, across the entire worm as it aged. They discovered a series of age-related changes in these events in different cell types, suggesting a previously unknown link between this mechanism and aging.
The new findings not only give researchers insight into aging on the molecular level, but the new open-access atlas and accompanying user-friendly data portal also serve as a resource for other researchers.