Publisher Health

Researchers have discovered that a protein called phosphorylated α-synuclein, which is associated with several neurodegenerative diseases such as Parkinson’s disease and Lewy body dementia, is also involved in the normal processes of how neurons communicate with each other in a healthy brain. The research, published in Neuron, was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health.
Phosphorylation is a process where a phosphate ion is added to a specific amino acid, or building block, of a protein, in this case the protein α-synuclein. This addition can change the shape of that protein, causing it to change its level of activity. Most studies of phosphorylated α-synuclein have studied its role in certain neurological disorders such as Parkinson’s disease and Lewy body dementia, where it builds up in protein clumps called Lewy bodies. These clumps are thought to be toxic to neurons, and one of the prevailing hypotheses is that the phosphorylation of the protein α-synuclein triggers these diseases.
“In most studies to date, the mere presence of α-synuclein phosphorylation is assumed to be a marker for pathology for certain disorders, like Parkinson’s and Lewy Body dementias,” said Beth-Anne Sieber, Ph.D., program director, NINDS. “Recently, there has been considerable interest in developing drugs that prevent α-synuclein phosphorylation as a way of treating these disorders. These findings challenge the current hypotheses about how these disorders may originate in the brain and may give insight into how we might better treat them.”
Previous work by the lab of Subhojit Roy, M.D., Ph.D., professor at the University of California, San Diego, and senior author of the study, suggested that in a healthy brain, the α-synuclein protein tones down excessive neuronal firing to regulate neuronal communication. While exploring this theory, Roy’s group unexpectedly found that phosphorylation was necessary for the normal function of α-synuclein.
Using a molecular modeling strategy to look at the structure of α-synuclein, Roy and his colleagues led by postdoctoral researcher Leonardo Parra-Rivas, Ph.D. discovered that when α-synuclein is phosphorylated, its structure changes in a way that promotes interactions with other proteins in healthy brains. Furthermore, they observed an association between increasing neural activity electrically or chemically and an increase in the amount of phosphorylated α-synuclein in both cultured cells and in mouse brain tissue. This finding suggests there might be a relationship between synaptic activity and α-synuclein phosphorylation.
Additionally, experiments show phosphorylation is necessary for α-synuclein to play its role in assembling a network of proteins that bind up synaptic vesicles — pockets that release chemicals enabling neurons to communicate with one another and other cells — and to slow neuronal activity. Therefore, phosphorylated α-synuclein acts almost as a brake or clutch mechanism to keep activity in certain neuronal circuits in check, suggesting that it might have a role in healthy brains, which had not previously been investigated.
“In hindsight, we hadn’t been looking at synuclein phosphorylation the right way,” said Roy. “Take for instance the circuits in the olfactory bulb, which according to our data has high levels of phosphorylated α-synuclein. The nose never stops smelling, so it needs to be active all the time. One hypothesis is that synuclein phosphorylation may have evolved as a safety mechanism to protect neuronal circuits that need to be hyperactive.”
The constant presence of α-synuclein phosphorylation in certain brain regions might reflect a need for this biochemical state in those areas. Additional studies are needed to understand how relatively low-frequency events in a healthy brain, when accumulated over a lifetime, can trigger the pathological accumulation of α-synuclein into Lewy bodies, leading to Parkinson’s disease and Lewy body dementias. Furthermore, therapies designed to block the phosphorylation of α-synuclein itself may need to consider the unintended adverse consequences of blocking a process that may help keep neurons functional during peak activity periods.
This work was funded by NINDS (NS111978, NS047101), the Farmer Family Foundation, Aligning Science Across Parkinson’s, and the Michael J. Fox Foundation for Parkinson’s Research.

A breakthrough study led by Dr. Mehdi Razavi at The Texas Heart Institute (THI), in collaboration with a biomedical engineering team of The University of Texas at Austin (UT Austin) Cockrell School of Engineering led by Dr. Elizabeth Cosgriff-Hernandez, sets the foundation of a ground-breaking treatment regimen for treating ventricular arrhythmia. Their study published in Nature Communications demonstrates the design and feasibility of a new hydrogel-based pacing modality.
The urgent need for an effective therapeutic regimen for ventricular arrhythmia inspired THI’s Electrophysiology Clinical Research & Innovations (EPCRI) team, led by its director, Dr. Razavi, to partner with Dr. Cosgriff-Hernandez and her UT Austin Biomedical Engineering (UT Austin BME) team to co-develop an innovative strategy that addresses the pathophysiology of re-entrant arrhythmia.
Ventricular arrhythmia, which occurs in the lower chambers of the heart or ventricles, is the leading cause of sudden cardiac death in the United States. When heart rhythm abnormality occurs in a self-sustained manner, it is called re-entrant arrhythmia, which is usually fatal.
“Re-entry occurs mainly from delayed conduction in scarred heart tissues, usually after coronary artery occlusion during a heart attack, which can be corrected by enabling pacing in these regions,” said Dr. Razavi, a practicing cardiologist and cardiac electrophysiologist. “These hydrogels then can access the scarred tissue, thereby enabling direct pacing of the otherwise inaccessible regions of the heart.”
Given hydrogels’ biostability, biocompatibility, tunable properties, and the ease of incorporating electrical conductivity, the scientists are exploring them as potential electrodes that can be easily delivered inside coronary veins. A clinical advantage of the unique system is that ischemia can be avoided by delivering the hydrogel using the veins.
The researchers successfully deployed the innovative hydrogel technology through minimally invasive catheter delivery in a pig model.
“The hydrogels have significant conductive properties that enable simultaneous pacing from multiple sites along the length of the hydrogel and create a conduction highway similar to those in Purkinje fibers,” according to Dr. Cosgriff-Hernandez.

Today, arrhythmia is treatable with medicines and procedures that control the irregular rhythms. The current anti-arrhythmic drugs on the market are not always effective; although the drugs slow the conduction velocity, they facilitate re-entry arrhythmia. Moreover, these drugs can be toxic and can lead to the destruction of tissues near the diseased regions of the heart. Even with the widely used interventional ablation therapies, arrhythmia recurs in a significant proportion of patients. None of these procedures address the mechanism of re-entry.
Cardiac defibrillators implanted to compensate for the shortfalls in the current therapy options are painful when delivering electric shocks to restore heart rhythm and can severely deteriorate the patient’s quality of life. If left untreated, arrhythmia can damage the heart, brain, or other organs, leading to stroke or cardiac arrest, during which the heart suddenly and unexpectedly stops beating.
“When injected into target vessels, the conductive hydrogel conforms to the patient’s vessel morphology. Adding a traditional pacemaker to this gel allows for pacing that resembles the native conduction in the heart — effectively mimicking the native electrical rhythm of the heart — and extinguishes the cause for arrhythmia, providing painless defibrillation,” added Dr. Cosgriff-Hernandez.
The work demonstrates for the first time the ability to confer direct electrical stimulation of the native and scarred mid-myocardium through injectable hydrogel electrodes as a pacing modality.
With minimally invasive catheter delivery and standard pacemaker technologies, this study indicates the feasibility of a novel pacing modality that resembles native conduction, potentially eliminating lethal re-entrant arrhythmia and providing painless defibrillation, which can be successfully adopted in a clinical workflow.
The scientific advance is significant considering pain management is highly relevant to overall wellness for patients with heart, lung, and blood diseases. Such innovation in painless defibrillation and preventing arrhythmia could revolutionize cardiac rhythm management.
Funding was provided by the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01 HL162741); Ford Pre-Doctoral Fellowship, administered by the National Academy of Science, Engineering and Medicine; Ford Dissertation Fellowship, administered by the National Academy of Science, Engineering and Medicine; Office of Vice President for Research, The University of Texas at Austin; The Roderick D. MacDonald Research Fund Award 19RDM004; and The Sultan Qaboos Chair in Cardiology at the St. Luke’s Foundation.

Like the Greek mythological beast with a snake’s tail and two ferocious heads, a potential Parkinson’s medicine created in the lab of chemist Matthew Disney, Ph.D., is also a type of chimera bearing two heads. One seeks out a key piece of Parkinson’s-causing RNA, while the other goads the cell to chop it to pieces for recycling.
The research is described in the Jan. 9 issue of the Proceedings of the National Academy of Sciences, or PNAS.
Parkinson’s is a frustrating and all too common disease. Slowly, people with Parkinson’s lose brain cells and other neurons needed to make the neurotransmitter dopamine. This progressive loss leads them to develop rigid, tense muscles and tremors, and causes difficulties with sleep, mood, speech, eating and movement.
Commonly used treatments include drugs that replace the dopamine. Other treatments, such as deep-brain stimulation, help with movement problems that develop as the disease worsens. But while these types of treatments alleviate symptoms, they are not a cure, come with side effects and do not change the trajectory of the disease. An estimated 500,000 people in the United States live with Parkinson’s.
“To change the course of this disease, we need to address its cause. For many Parkinson’s patients, that apparent cause is the accumulation of a toxic protein called alpha-synuclein, in and around their neurons,” said Disney, the endowed Institute Professor and chair of the chemistry department at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology in Jupiter, Florida.
Unfortunately, alpha-synuclein has proven an especially challenging protein to medicate due to its unruly, disorganized form and lack of clear druggable structures, Disney added.
“In situations like this, we have found that targeting the RNA needed to build the toxic protein may be an optimal strategy to slowing or even stopping disease progression,” he added.

Disney’s lab focuses on interfering with or degrading RNA needed to assemble the proteins implicated in disease. This is a relatively new concept. Most drugs on the market work by binding to proteins to change their function. But not all disease-causing proteins can be successfully targeted with drugs. Some are too changeable, some lack druggable structures, some fold in a way that conceals their active sites.
Disney’s approach is to prevent the problematic proteins from being made in the first place. To do that requires targeting their RNA. Here’s why: Proteins are assembled in cells through a process that involves the reading and translation of a gene, the transport of that information from the cell nucleus to its cytoplasm via messenger RNA, and the assembly of protein-building factories called ribosomes, also built of RNA, in the cytoplasm. The ribosomes stitch the proteins together one amino acid at a time. Disney’s potential Parkinson’s drug, which he calls Syn-RiboTAC, binds to a section of messenger RNA that tells a ribosome to start protein assembly. Without the “start” signal, the toxic protein isn’t built.
Disney’s first authors on the PNAS study were graduate students in his lab. Yuquan Tong is a current student of the Skaggs Graduate School of Chemical and Biological Sciences on the Jupiter, Florida campus, and Peiyuan Zhang, Ph.D., is a recent graduate, now a postdoctoral researcher at the Massachusetts Institute of Technology.
“In Parkinson’s mouse models, we see that reducing alpha-synuclein by even 25% is therapeutically beneficial,” Tong said. “In studies from induced neurons of Parkinson’s patients, we see the Syn-RiboTAC strategy reduces alpha-synuclein production by about 50%. We saw that adding the RiboTAC produces a significant gain in potency.”
Disney added that the compound also showed good selectivity, important for avoiding unwanted side effects, and improved brain-barrier penetration relative to other compounds they studied.
Other collaborators on the study included physician-scientist M. Maral Mouradian, M.D., of Rutgers University, whose patients donated tissue to create induced neurons.
Much work lies ahead, as the team works to refine the two-headed drug and improve its drug-like properties, the scientists said. Preparing an experimental compound for clinical trials in humans can sometimes take years, as refinements are made and data are gathered.
“The medical need for a truly disease-modifying treatment is significant, and we know that patients are awaiting better options,” Disney said. “We’re hopeful that we’re on the road to a better days for people living with Parkinson’s.”

For patients with multiple sclerosis, a regular exercise routine is important for managing symptoms. Due to different causes of chronic pain though, physical exercise can be more difficult for some.
Research published in the Journal of Pain from the University of Michigan found that widespread pain with nociplastic features, also known as WPNF, can make engaging in physical activity a painful task for some patients with MS.
“WPNF is a chronic and diffuse pain which can be challenging to localize or describe precisely,” said Libak Abou, Ph.D., Research Assistant Professor and lead author of the paper.
“In a person with MS, this type of pain arises from altered processing signals within the central nervous system. This is opposed to pain that arises from specific tissue damage, classified as nociceptive pain, or pain related to demyelination and axonal damage, classified as neuropathic pain.”
Abou and fellow researchers surveyed patients with MS to see if those with a higher indication of WPNF were more likely to be insufficiently active or sedentary when compared to their MS counterparts with no chronic pain, nociceptive pain, or neuropathic pain. Each of the participants was self-reporting with their data.
The results of the survey showed that those who experienced WPNF in addition to their MS were not sufficiently active due to the chronic pain they were experiencing.
“There is a growing need to consider what type of pain MS patients are experiencing before giving them an exercise plan,” said Abou. “The concept of considering WPNF when creating exercise plans for MS is newer but could help many patients get to an activity level that will help ease symptoms without causing them intense pain.”
For the future, Abou hopes that clinicians can begin doing screenings for underlying pain mechanisms in patients with MS that are struggling to stay active to help further tailor their physical routines to their personal needs.
“The end goal is to help those with MS maintain their functional independence,” said Abou. “It is also important to remember that these patients will likely need extra support from their physical therapy team to keep them on a path with less pain.”
Additional authors: Libak Abou, Daniel Whibley, and Anna L. Kratz from the Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, Michigan as well as the Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan. Daniel J. Clauw from the Department of Anesthesiology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

UCLA-led research finds that scooter injuries nearly tripled across the U.S. from 2016 to 2020, with a concurrent increase in severe injuries requiring orthopedic and plastic surgery over the same period.
The study, which compared national trends in scooter and bicycle injuries during the period, also found that costs to treat those injuries rose five-fold, highlighting the financial strain these injuries pose to the healthcare system — a finding that “underscores a critical juncture for discerning the underlying causes of injuries and informing policies for injury prevention,” the researchers note.
The study will be published January 9 in the peer-reviewed Journal of the American College of Surgeons.
“Considering the rise in the number of hospitalizations and major operations for scooter-related injuries, it’s crucial to elevate safety standards for riders,” said lead author Nam Yong Cho, a third-year medical student at UCLA and a research associate at the UCLA Cardiovascular Outcomes Research Laboratories. “Advocating for improved infrastructure, including enforced speed limits and dedicated lanes, is also vital to minimize risks for vehicles, scooter riders, and pedestrians alike.”
The researchers used the 2016-2020 National Inpatient Sample, a database maintained by the Agency for Healthcare Research and Quality, to compare trends and outcomes for scooter-related and bicycle-related injuries. The database does not, however, differentiate between electric and non-electric scooters. Of nearly 93,000 patients who were hospitalized for injuries, about 6,100 (6.6%) resulted from scooter injuries.
Overall, about 27% of people in the scooter cohort were under age 18 compared with 16% for the bicycle group. In addition, injuries were most frequent in the winter months (24% vs 20%), patients were insured by Medicaid (27% vs 24%); and scooter injuries led to more major operative interventions (56% vs 48%), which mainly included orthopedic and plastic surgery (89% vs 85%) and operations to the head (5% vs 4%).
Scooter riders also had higher odds of experiencing long bone fractures and paralysis than their bicycle riding counterparts, though both groups were similarly likely to suffer traumatic brain injuries.

Finally, the annual healthcare burden of treating scooter-related injuries jumped from about $6.6 million in 2016 to $35.5 million in 2020. For bicycle injuries, the price tag increased from $307 million to $434 million.
The study has some limitations. They include a limited amount of granular data such as helmet use, presence of multiple riders on the vehicles, and use of intoxicants; and an inability to account for objects and other vehicles that might have been involved in the injury incidents, or to determine the kind of terrain where they happened, and speed, time of day and total distance traveled when they occurred. The researchers also could not ascertain the type of scooter or bicycle models involved in the injuries.
Still, the findings indicate a worrisome increase in patient injury, hospitalization and financial burden, the researchers note.
“The progressive exacerbation of injury severity in scooter-related incidents manifested in a substantial proportion of patients necessitating surgical intervention and potentially having long-term morbidity,” the researchers write. “Our findings are a call to action for healthcare leaders to empower themselves in promoting scooter-related injury prevention and greater safety in the community.”
Study co-authors are Shineui Kim, Dr. Zachary Tran, Dr. Joseph Hadaya; Konmal Ali, Elsa Kronen and Dr. Peyman Benharash of UCLA, and Dr. Sigrid Burruss of Loma Linda University Health. Tran is also affiliated with Loma Linda University Health.

Researchers from the University of Tsukuba have discovered that estrogen receptor (ER) β, expressed in the lateral septum of the limbic system, plays a crucial role in suppressing anxiety-like behavior exhibited by male mice in social situations. They also discovered that the distribution and expression region of ERβ differs from that of ERα.
Estradiol (E2), a sex steroid hormone, plays an essential role in social behavior, including regulating social anxiety, which is anxiety experienced when unknown individuals are encountered. In males, testosterone secreted by the testes is converted to E2 in the brain, and the E2 binds to two types of estrogen receptors (ERs), ERα and ERβ, to regulate social behavior. However, its neuroendocrine basis has not been understood. In this study, the role of ERα and ERβ expressed in the lateral septum (LS), which regulates social anxiety, was investigated using male mice.
The researchers first investigated the expression of ERα and ERβ in LS using genetically modified male mice. ERβ-expressing cells in the mice were labeled with red fluorescent protein, which revealed that the distributions of ERα and ERβ are different. Furthermore, the researchers investigated the knockdown effects of ERα or ERβ gene expression in the LS of male mice during situations of social and nonsocial anxiety. The results show that social anxiety increases with the inhibition of ERβ expression. Additionally, ERα- and ERβ-positive cells in the LS projected into different regions of the hypothalamus. Thus, the researchers concluded that ERα- and ERβ-expressing cells in LS are distinct cell populations with different localizations and neuronal projections, and the ERβ population plays a crucial role in neural circuitry that regulates anxiety-like behavior in social situations.
This work was supported by grant-in-aid for Scientific Research 15H05724, 21K18547, and 22H02941 to SO.

A combination of only 11 proteins can predict long-term disability outcomes in multiple sclerosis (MS) for different individuals. The identified proteins could be used to tailor treatments to the individual based on the expected severity of the disease. The study, led by researchers at Linköping University in Sweden, has been published in the journal Nature Communications.
“A combination of 11 proteins predicted both short and long-term disease activity and disability outcomes. We also concluded that it’s important to measure these proteins in cerebrospinal fluid, which better reflects what’s going on in the central nervous system, compared with measuring in the blood,” says Julia Åkesson, doctoral student at Linköping University and the University of Skövde.
In multiple sclerosis, the immune system attacks the person’s own body, damaging nerves in the brain and in the spinal cord. What is attacked primarily is a fatty compound called myelin, which surrounds and insulates the nerve axons so that signals can be transmitted. When myelin is damaged, transmission becomes less efficient.
Disease progression in multiple sclerosis varies considerably from person to person. To those for whom a more severe disease is predicted, it is important not to lose valuable time at the onset of the disease but to get the right treatment quickly. The researchers behind the current study, which is a collaboration between Linköping University, the Karolinska Institute and the University of Skövde, wanted to find out whether it was possible to detect at an early stage of disease which patients would require a more powerful treatment. Being able to do so would be relevant both to physicians and those living with MS.
“I think we’ve come one step closer to an analysis tool for selecting which patients would need more effective treatment in an early stage of the disease. But such a treatment may have side effects and be relatively expensive, and some patients don’t need it,” says Mika Gustafsson, professor of bioinformatics at the Department of Physics, Chemistry and Biology at Linköping University, who led the study.
Finding markers linked to disease severity many years ahead is a complicated challenge. In their study, the researchers analysed nearly 1,500 proteins in samples from 92 people with suspected or recently diagnosed MS. Data from the protein analyses were combined with a large amount of information from the patients’ journals, such as disability, results from MRI scans of the nervous system, and treatments received. Using machine learning, the researchers found a number of proteins that could predict disease progression.
“Having a panel consisting of only 11 proteins makes it easy should anyone want to develop analysis for this. It won’t be as costly as measuring 1,500 proteins, so we’ve really narrowed it down to make it useful for others wanting to take this further,” says Sara Hojjati, doctoral student at the Department of Biomedical and Clinical Sciences at Linköping University.

The research team also found that a specific protein, leaking from damaged nerve axons, is a reliable biomarker for disease activity in the short term. This protein is called neurofilament light chain, NfL. These findings confirm earlier research on the use of NfL to identify nerve damage and also suggest that the protein indicates how active the disease is.
One of the main strengths of the study is that the combination of proteins found in the patient group from which samples were taken at Linköping University Hospital was later confirmed in a separate group consisting of 51 MS patients sampled at the Karolinska University Hospital in Stockholm.
This study is the first to measure such a large amount of proteins with a highly sensitive method, proximity extension assay, combined with next-generation sequencing, PEA-NGS. This technology allows for high-accuracy measuring also of very small amounts, which is important as these proteins are often present in very low levels.
The study was funded by the Swedish Foundation for Strategic Research, the Swedish Brain Foundation, Knut and Alice Wallenberg Foundation, Margaretha af Ugglas Foundation, the Swedish Research Council, NEURO Sweden and the Swedish Foundation for MS research, and others.

More than 65,000 men fall ill with prostate cancer each year in Germany. Twelve thousand of them develop a treatment-resistant form which eventually ends in death. Now, a team of researchers from the Medical Faculty at the University of Freiburg has developed an active substance that might in future represent a new treatment option. This substance, known as KMI169, targets an enzyme that plays an important role in the development of prostate cancer. The inhibitor displayed massive potential in among others cancer cells that were resistant to conventional treatments.
Researchers from the Department of Urology at the Freiburg University Medical Center as well as the Institut für Pharmazeutische Wissenschaften at the University of Freiburg published their study in Nature Communications on 2 January 2024.
“We’ve had our eye on the enzyme KMT9 as a possible target in prostate cancer for a long time. The development of this specific inhibitor is now a decisive step in combating prostate cancer far more effectively,” explains study head Professor Roland Schüle, Academic Director of the Department of Urology at the Freiburg University Medical Center and Dr. Eric Metzger, group leader in Schüle’s department.The substance’s potential use against treatment-resistant forms of cancer makes it especially valuable. “This treatment-resistance means that the classic antihormonal treatment often fails within a few months and the disease then progresses rapidly. The inhibitor we’ve developed offers us a highly innovative therapeutic approach here,” says Schüle.
New approach also relevant to bladder cancer
Using cell cultures, the groups headed by Schüle and co-author Professor Manfred Jung, head of the Chemical Epigeneticsgroup of the Institut für Pharmazeutische Wissenschaften, have shown that the enzyme KMT9, known as a methyltransferase, is a critical factor in the development and progress of certain types of cancer such as prostate or bladder cancer. “The inhibitor fits snugly like a key in its lock and blocks the functioning of KMT9 and therefore also the growth of both prostate and bladder cancer cells,” says Jung. The development of KMI169 was guided by crystal structure analysis of KMT9 and numerous other studies. “We modified the compound many times to increase its potency, selectivity and medicinal properties.”

Models used by scientists to predict how epidemics will spread have a major flaw since they do not take into account the structure of the networks underlying transmission.
According to a new study from the University of Birmingham, modelling used to forecast the effects of diseases, such as Covid-19, can significantly overestimate the number of infections that will occur in an epidemic “wave.”
The research, published today (9th January) in the Journal of Physics: Complexity¸ comes as the Covid inquiry continues to investigate what went wrong with the Government’s handling of the pandemic, and what should be done better in the future.
Currently, epidemic modelling does not usually factor in that people are connected by a network of contacts where transmission might occur. Instead, many of these models, such as the ones that were used to inform decisions concerning Covid-19, make the assumption of “random mixing.”
Dr Samuel Johnson, Associate Professor in Applied Mathematics at the University of Birmingham, who conducted the study said: “It has been known for a long time that the properties of social networks are important for epidemic spreading, we can see this in action when those who were exposed to Covid-19 through mixing with infected individuals were contacted to let them know of their exposure. But because we do not have a way of knowing the whole network of millions of people, modellers usually do the best they can and assume random mixing, i.e. that anyone could infect anyone else. The problem is that the properties of this network can completely change the outcomes predicted.”
The research considers that if these networks are heterogeneous, meaning that some people have a lot more contacts than others, then epidemic “waves” may be much smaller than predicted by standard models. Dr Johnson continues: “This is partly because fewer people get infected for a given transmissibility. But also, if you look at data on infections through a random-mixing lens you will overestimate transmissibility, and these two errors compound each other.”
In the paper, a simple version of these models shows two epidemic waves looking initially the same, but in the random-mixing case nearly 90% of people eventually become infected, whereas on a “scale free” (heterogeneous) network it is only 20%.

Dr Johnson also explores how changes in networks over time can lead to multiple waves of an epidemic, even after “herd immunity” has apparently been reached with previous waves. These findings might explain some of the big mistakes that groups modelling the pandemic seem to have made.
“Not everyone has the same numbers of friends, family, and colleagues, or goes out to places where large groups of people may be present,” explained Dr Johnson. “And the fact that superspreader events play such a significant role in the early stages of an epidemic supports the hypothesis that the real network of contacts is, like many other social networks, highly heterogeneous.”
The study argues that the structure of social networks cannot be ignored if epidemic modelling is to make useful predictions.
Dr Johnson concluded: “Taking social networks into account should be a fundamental part of epidemic modelling. Even if we do not know what the network is like in detail, it still might be better to factor in that it is probably heterogeneous. And it is certainly preferable to realise we have this uncertainty, rather than assuming that, because we have put lots of other ingredients into our models, they will make useful crystal balls.
“As the political psychodrama of the Covid Inquiry continues to be played out in the news, it is important to note that the government, scientists, and wider society should be learning from what went wrong during the pandemic, and what went well. For example, rather than focusing on who said what in the UK, we could be comparing what happened in other countries when different measures were implemented. We need to make improvements so that we are ready for when the next one comes along, and working out how to account for social networks in epidemic modelling would be a big first step.”

A high-sugar diet is bad news for humans, leading to diabetes, obesity and even cancer. Yet fruit bats survive and even thrive by eating up to twice their body weight in sugary fruit every day.
Now, UC San Francisco scientists have discovered how fruit bats may have evolved to consume so much sugar, with potential implications for the 37 million Americans with diabetes. The findings, published on Tuesday, Jan. 9, 2024 in Nature Communications, point to adaptations in the fruit bat body that prevent their sugar-rich diet from becoming harmful.
Diabetes is the eighth leading cause of death in the United States, according to the Centers for Disease Control and Prevention, and it’s responsible for $237 billion in direct medical costs each year.
“With diabetes, the human body can’t produce or detect insulin, leading to problems controlling blood sugar,” said Nadav Ahituv, PhD, director of the UCSF Institute for Human Genetics and co-senior author of the paper. “But fruit bats have a genetic system that controls blood sugar without fail. We’d like to learn from that system to make better insulin- or sugar-sensing therapies for people.”
Ahituv’s team focused on evolution in the bat pancreas, which controls blood sugar, and the kidneys. They found that the fruit bat pancreas, compared to the pancreas of an insect-eating bat, had extra insulin-producing cells as well as genetic changes to help it process an immense amount of sugar. And fruit bat kidneys had adapted to ensure that vital electrolytes would be retained from their watery meals.
“Even small changes, to single letters of DNA, make this diet viable for fruit bats,” said Wei Gordon, PhD, co-first author of the paper, a recent graduate of UCSF’s TETRAD program, and assistant professor of biology at Menlo College. “We need to understand high-sugar metabolism like this to make progress helping the one in three Americans who are prediabetic.”
A sweet tooth without consequences
Each day, after 20 hours of sleep, fruit bats wake up for four hours to gorge on fruit. Then it’s back to the roost.

To understand how a fruit bat pulls off this feat of sugar consumption, Ahituv and Gordon collaborated with scientists from a variety of institutions, ranging from Yonsei University in Korea to the American Museum of Natural History in New York City, to compare the Jamaican fruit bat to the big brown bat, which only eats insects.
The researchers analyzed gene expression (which genes were on or off) and regulatory DNA (the parts of DNA that control gene expression) using a method for measuring both in individual cells.
“This newer single-cell technology can explain not only which types of cells are in which organs, but also how those cells regulate gene expression to manage each diet,” Ahituv said.
In fruit bats, the compositions of the pancreas and kidneys evolved to accommodate their diet. The pancreas had more cells to produce insulin, which tells the body to lower blood sugar, as well as more cells to produce glucagon, the other major sugar-regulating hormone. The fruit bat kidneys, meanwhile, had more cells to trap scarce salts as they filter blood.
Zooming in, the regulatory DNA in those cells had evolved to turn the appropriate genes for fruit metabolism on or off. The big brown bat, on the other hand, had more cells for breaking down protein and conserving water. And the gene expression in those cells was tuned to handle a diet of bugs.
“The organization of the DNA around the insulin and glucagon genes was very clearly different between the two bat species,” Gordon said. “The DNA around genes used to be considered ‘junk,’ but our data shows that this regulatory DNA likely helps fruit bats react to sudden increases or decreases in blood sugar.”
While some of the biology of the fruit bat resembled what’s found in humans with diabetes, the fruit bat appeared to evolve something that humans with a sweet tooth could only dream of: a sweet tooth without consequences.

“It’s remarkable to step back from model organisms, like the laboratory mouse, and discover possible solutions for human health crises out in nature,” Gordon said. “Bats have figured it out, and it’s all in their DNA, the result of natural selection.”
Superheroes of evolution
The study benefited from a recent groundswell of interest in studying bats to better human health. Gordon and Ahituv traveled to Belize to participate in an annual Bat-a-Thon with nearly 50 other bat researchers, taking a census of wild bats as well as field samples for science. One of the Jamaican fruit bats captured at this event was used in the sugar metabolism study.
As one of the most diverse families of mammals, bats include many examples of evolutionary triumph, from their immune systems to their peculiar diets and beyond.
“For me, bats are like superheroes, each one with an amazing super power, whether it is echolocation, flying, blood sucking without coagulation, or eating fruit and not getting diabetes,” Ahituv said. “This kind of work is just the beginning.”
Key collaborators included co-first author Seungbyn Baek, PhD, from Yonsei University (South Korea); co-senior author Martin Hemberg, PhD, from Harvard Medical School; Tony Schountz, PhD, from Colorado State University; Lisa Noelle Cooper, PhD, from Northeast Ohio Medical University; Melissa R. Ingala, PhD, Fairleigh Dickinson University; and Nancy B. Simmons, PhD, American Museum of Natural History. Other UCSF authors are Hai P. Nguyen, PhD, Yien-Ming Kuo, PhD, Rachael Bradley, and Sarah L. Fong, PhD. For all authors see the paper.