Spinocerebellar ataxia 4 is a devastating progressive movement disease that can begin as early as the late teens. Now, a multinational research team led by University of Utah researchers has conclusively identified the genetic difference that causes the disease, bringing answers to families and opening the door to future treatments.
Some families call it a trial of faith. Others just call it a curse. The progressive neurological disease known as spinocerebellar ataxia 4 (SCA4) is a rare condition, but its effects on patients and their families can be severe. For most people, the first sign is difficulty walking and balancing, which gets worse as time progresses. The symptoms usually start in a person’s forties or fifties but can begin as early as the late teens. There is no known cure. And, until now, there was no known cause.
Now, after 25 years of uncertainty, a multinational study led by Stefan Pulst, M.D., Dr. med., professor and chair of neurology, and K. Pattie Figueroa, a project manager in neurology, both in the Spencer Fox Eccles School of Medicine at University of Utah, has conclusively identified the genetic difference that causes SCA4, bringing answers to families and opening the door to future treatments. Their results are published in the peer-reviewed journal Nature Genetics.
Solving a genetic enigma
SCA4’s pattern of inheritance had long made it clear that the disease was genetic, and previous research had located the gene responsible to a specific region of one chromosome. But that region proved extraordinarily difficult for researchers to analyze: full of repeated segments that look like parts of other chromosomes, and with an unusual chemical makeup that makes most genetic tests fail.
To pinpoint the change that causes SCA4, Figueroa and Pulst, along with the rest of the research team, used a recently developed advanced sequencing technology. By comparing DNA from affected and unaffected people from several Utah families, they found that in SCA4 patients, a section in a gene called ZFHX3 is much longer than it should be, containing an extra-long string of repetitive DNA.
Isolated human cells that have the extra-long version of ZFHX3 show signs of being sick — they don’t seem able to recycle proteins as well as they should, and some of them contain clumps of stuck-together protein.

“This mutation is a toxic expanded repeat and we think that it actually jams up how a cell deals with unfolded or misfolded proteins,” says Pulst, the last author on the study. Healthy cells need to constantly break down non-functional proteins. Using cells from SCA4 patients, the group showed that the SCA4-causing mutation gums up the works of cells’ protein-recycling machinery in a way that could poison nerve cells.
Hope for the future
Intriguingly, something similar seems to be happening in another form of ataxia, SCA2, which also interferes with protein recycling. The researchers are currently testing a potential therapy for SCA2 in clinical trials, and the similarities between the two conditions raise the possibility that the treatment might benefit patients with SCA4 as well.
Finding the genetic change that leads to SCA4 is essential to develop better treatments, Pulst says. “The only step to really improve the life of patients with inherited disease is to find out what the primary cause is. We now can attack the effects of this mutation potentially at multiple levels.”
But while treatments will take a long time to develop, simply knowing the cause of the disease can be incredibly valuable for families affected by SCA4, says Figueroa, the first author on the study. People in affected families can learn whether they have the disease-causing genetic change or not, which can help inform life decisions such as family planning. “They can come and get tested and they can have an answer, for better or for worse,” Figueroa says.
The researchers emphasize that their discoveries would not have been possible without the generosity of SCA4 patients and their families, whose sharing of family records and biological samples allowed them to compare the DNA of affected and unaffected individuals. “Different branches of the family opened up not just their homes but their history to us,” Figueroa says. Family records were complete enough that the researchers were able to trace the origins of the disease in Utah back through history to a pioneer couple who moved to Salt Lake Valley in the 1840s.
Since meeting so many families with the disease, studying SCA4 has become a personal quest, Figueroa adds. “I’ve been working on SCA4 directly since 2010 when the first family approached me, and once you go to their homes and get to know them, they’re no longer the number on the DNA vial. These are people you see every day… You can’t walk away. This is not just science. This is somebody’s life.”
This work was performed in collaboration with researchers from University of Tübingen, University of Lübeck and Kiel University, University Hospital Hamburg-Eppendorf, and Veterans Administration Medical Center, Albany, NY.
The study was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R35127253 and the DFG-funded INST 37/1049-1.

Brown fat, also known as brown adipose tissue (BAT), is a type of fat in our bodies that’s different from the white fat around our belly and thighs that we are more familiar with. Brown fat has a special job — it helps to burn calories from the foods that we eat into heat, which can be helpful, especially when we’re exposed to cold temperatures like during winter swimming or cryotherapy. For a long time, scientists thought that only small animals like mice and newborns had brown fat. But new research shows that a certain number of adults maintain their brown fat throughout life. Because brown fat is so good at burning calories, scientists are trying to find ways to activate it safely using drugs that boost its heat-producing abilities.
A new study from the research groups of Prof. Jan-Wilhelm Kornfeld from the University of Southern Denmark/the Novo Nordisk Center for Adipocyte Signaling (Adiposign) and Dagmar Wachten from the University Hospital Bonn and the University of Bonn (Germany) has found that brown fat has a previously unknown built-in mechanism that switches it off shortly after being activated. This limits its effectiveness as treatment against obesity. According to first author of the study, Hande Topel, who is a Senior Postdoc at the University of Southern Denmark and the Novo Nordisk Center for Adipocyte Signaling (Adiposign), the team has now discovered a protein responsible for this switching-off process. It is called ‘AC3-AT’.
Blocking the “off switch” opens up a new strategy
“Looking ahead, we think that finding ways to block AC3-AT could be a promising strategy for safely activating brown fat and tackling obesity and related health problems,” Hande Topel says. The research team found the switch-off protein using advanced technology predicting unknown proteins. Hande Topel explains: “When we investigated mice that genetically didn’t have AC3-AT, we found that they were protected from becoming obese, partly because their bodies were simply better at burning off calories and were able to increase their metabolic rates through activating brown fat.”
Two groups of mice were fed a high-fat diet for 15 weeks, which rendered them obese. The group that had their AC3-AT protein removed, gained less weight than the control group and were metabolically healthier. “The mice that have no AC3-AT protein, also accumulated less fat in their body and increased their lean mass when compared to the control mice,” says co-author, Ronja Kardinal, who is a PhD student at the University of Bonn in the lab of Dagmar Wachten at UKB, continuing: “As AC3-AT is found not only in mice but also in humans and other species, there are direct therapeutic implications for humans.”
Hope for strategies that support weight loss
Although the prevalence of brown fat decreases as humans age, and despite grown-ups not having as much brown fat as newborns, it can still be activated, for instance by cold exposure. When it gets activated, it enhances the rate of metabolism of these individuals, which again may help to stabilize weight loss in conditions where calorie intake is (too) high.

Intriguingly, this study not only identified AC3-AT, which is a shorter, previously unknown form of the AC3protein. The researchers also identified other unknown protein/gene versions, that respond to cold exposure, similar to AC3-AT.
“However, further research is needed to elucidate the therapeutic impact of these alternative gene products and their regulatory mechanisms during BAT activation,” says co-corresponding author Prof. Dagmar Wachten, Co-Director of the Institute of Innate Immunity at the UKB and member of the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Areas (TRA) “Modelling” and “Life & Health” at the University of Bonn.
“Understanding these kinds of molecular mechanisms not only sheds light on the regulation of brown fat but also holds promise for unraveling similar mechanisms in other cellular pathways. This knowledge can be instrumental in advancing our understanding of various diseases and in the development of novel treatments,” says co-corresponding author Prof. Jan-Wilhelm Kornfeld, University of Southern Denmark.
This study was conducted in the context of the DFG Collaborative Research Center Transregio-SFB 333 “Brown and Beige Fat — Organ Interactions, Signaling Pathways and Energy Balance (BATenergy),” which is pursuing a better understanding of the different types of adipose tissue and their role in metabolic diseases and the Novo Nordisk Foundation Center for Adipocyte Signaling (Adiposign) at University of Southern Denmark that aims to understand fat cell dysfunction in model organisms and obese patients.

GNC and the Vitamin Shoppe are redesigning displays and taking other steps to appeal to people who are taking or are interested in drugs like Ozempic and Wegovy.As diabetes and weight-loss drugs like Ozempic and Wegovy took off in the last few years, many people turned away from established diet and nutrition products.Now, two retailers that specialize in nutritional supplements — GNC and the Vitamin Shoppe — are trying new approaches to win over people who are taking those drugs or who are interested in them.GNC is dedicating a wall of supplements in its more than 2,300 stores to products that it believes will appeal to people on Ozempic, which contains the compound semaglutide, and other drugs that are known as GLP-1 medicines. The chain is also training workers to help customers assess which substances could help them manage common side effects of those prescription drugs.Michael Costello, chief executive of GNC, said his company saw a “big opening” in helping individuals taking such drugs for weight loss.“As we were looking at the trends with folks, where people are going, Ozempic and obviously Wegovy and other GLP-1s started blowing up,” Mr. Costello said in an interview. “We saw there were significant side effects for a lot of those drugs.”It’s not clear exactly how many Americans are taking Ozempic and similar drugs for weight loss, but Mr. Costello referred to a study from Goldman Sachs that estimates up to 70 million Americans will have tried the medicines by 2028.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Published42 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PacemakerBy Marie-Louise ConnollyBBC News NI health correspondent”Watching Covid patients say goodbye to their families via a Zoom call was difficult and extremely emotional.”Dr George Gardiner was an intensive care consultant at the Royal Victoria Hospital in Belfast and treated the most critically ill in the pandemic. He says health staff who held a phone or iPad for patients and their loved ones witnessed “harrowing scenes” before a ventilator was turned off.This week the UK Covid inquiry arrives in Northern Ireland. Why decisions were taken about what happened in hospitals, care homes and how people were buried and who made those decisions will all be investigated.’Losing Mum and Dad to Covid still seems unreal’Politicians lack humanity, Covid daughter saysCovid warning as hospital admissions riseUK Covid inquiry in Northern Ireland On Tuesday, the UK Covid inquiry which is sitting in Belfast for three weeks will start hearing from the most senior politicians and health advisors in Northern Ireland about why decisions were taken and by whom. This is module 2c of the inquiry, which is focussing on decision-making and political governance.This module will investigate Northern Ireland specifically and will include the initial response, central government decision making, and political and civil service performance.It will also probe whether Northern Ireland’s political nuances had any affect on the effectiveness of the response.There were tensions between the political parties when senior Sinn Féin figures attended the funeral of ex-IRA leader Bobby Storey and when the DUP’s Edwin Poots, then minister for Agriculture, Environment and Rural Affairs, said coronavirus was more common in nationalist areas.Who will appear at the Covid inquiry in Northern Ireland?The hearings begin with opening statements and evidence from Covid-19 Bereaved Families and Disability Action. Core participants who have been named in advance include the former first ministers, Dame Arlene Foster and Paul Givan, and Michelle O’Neill, who was deputy first minster during the pandemic. Senior representatives from the departments of health, finance, the Executive Office, and the civil service will also be questioned. Specific names and when they will appear are released weekly.Other people appearing this week will be Eddie Lynch, the Commissioner for Older People, Sir David Sterling, former head of the Northern Ireland Civil Service, and Jayne Brady the current head of the NI Civil Service.Image source, PacemakerBereaved Families for Justice Northern Ireland Brenda Doherty, whose mum Ruth Burke was the fourth person to die in Northern Ireland with Covid-19 is among those leading the local bereaved Families for Justice Group. “Families were failed. We have always said this inquiry is about learning lessons so that nobody should go through again what we did. This is a living hell,” she said.”We had to meet my mum’s coffin at the cemetery gates. We weren’t allowed to touch it -we had to stand away from it and were told we could move closer once the coffin was in the hole.”Ms Doherty, who gave evidence at the Covid Inquiry in London, said she will judge the inquiry after it finishes its hearings in Northern Ireland. “There is already a lot of confidence lost in politicians,” she said. “I think this is their time to show that they can be open and honest and take ownership of the mistakes that were made because there were mistakes.Image source, Brenda Doherty”I don’t want to hear ‘I can’t recall’, or ‘I don’t remember’ because for me it shouldn’t be a matter of recalling – if you were making decisions that were impacting people’s lives there is bound to be paperwork somewhere and if you can’t find the paper work well then something is not right.” Speaking to BBC News NI, Ms Doherty said the inquiry needs to help people cope with loss. “We have all suffered loss – it is like somebody came and took them and for families who lost both parents it is like they have just vanished,” she said. “My sister says it is like somebody stole Mummy in the middle of the night because we didn’t get to see her when she died or in the coffin.”Analysis: An important three weeksThe next three weeks will be important for Northern Ireland. The UK Covid inquiry will be shining a light on the key decisions made by senior politicians and health officials. In March 2020, the Northern Ireland Executive had once again been rebooted.Relations between politicians and the state of the health and social care service were both fragile. While Northern Ireland fared comparatively better than the rest of the UK in terms of Covid deaths (5060), those families who did lose loved ones want and deserve answers. These hearings will scrutinise the political tensions that developed in the executive, certain headline events that caused political parties to publicly fall out and whether all of that impacted on how the public kept to the rules.Who is leading the Covid inquiry and how does it work?The Covid inquiry began on 28 June 2022 and is chaired by former judge Baroness Hallett who led the inquests into the 7 July London Bombings. Image source, PA MediaThe inquiry has already had public hearings on resilience and preparedness; the current module 2c hearings are examining core UK decision-making and political governance. Sitting in Belfast and focussing on what happened in Northern Ireland is significant as it means local politicians and health officials will be probed and the evidence they’ve provided to the inquiry, including WhatsApp messages and emails, will be questioned and shared publicly. When will the inquiry publish conclusions?Baroness Hallett said she intends to publish the report for the first area of work by early summer 2024.The inquiry is not expected to conclude until sometime in 2026.Public hearings for the third area of examination – the impact of the pandemic on healthcare systems across the UK – are expected to run for 10 weeks from autumn 2024. How can the public get involved? Anyone can share their experience through the inquiry’s Every Story Matters project.The Covid-19 Bereaved Families for Justice campaign group – which criticised the government’s handling of the pandemic – has urged the inquiry to ensure these voices are heard.Jennifer Currie’s mother June died in hospital in 2020 after contracting Covid while she was being treated for cellulitis. The family say the circumstances around their mother’s death “haunts them” as they were never informed that she was receiving end of life care. While some of the family had a brief visit on the day she died, Jennifer said they would have insisted staying in the hospital even in the car park to be close by.”When we went to leave, she said to us please don’t leave me I am going to die and that will stay with us forever. Had we had known that my mum was in end of life care – we would never have walked out of that hospital,” Jennifer said. It is hoped the inquiry will listen and learn from those who have provided stories and who are providing evidence. Dr Gardiner said he hoped that if there is another pandemic, lessons will be learned about how a twin track approach can operate within the health service where other patients with serious health conditions including cancer can continue with treatment. More on this storyFamily was told Covid would be ‘flash in the pan’Published18 July 2023What is the UK Covid inquiry and how does it work?Published3 days agoAlmost £8bn spent on NI’s response to Covid-19Published27 July 2023

Published12 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Becky MortonPolitical reporterThe Liberal Democrats have called for everyone over 70 or with a long-term health condition in England to get access to a named GP. The party said a “return to the family doctor” would help avoid hospital appointments and save the NHS money.Patients in England over 70 have had a named GP since 2013, with this extended to all patients in 2015. But Lib Dem leader Sir Ed Davey told the BBC this was “a tick-box exercise” that had not been implemented. The Conservative Party said the “huge unfunded spending commitment” from the Liberal Democrats was “just another empty promise”. The Liberal Democrats said their policy would ensure over-70s and those with long-term health conditions – an estimated 18.7 million people – would be offered appointments with their named GP as a first option wherever possible. It said these groups had been found to benefit the most from having access to the same GP. The Lib Dems have already pledged to give everyone a legal right to see a GP within a week or 24 hours if in urgent need. Sir Ed said: “We want to see the return of the family doctor, so patients with long-term care needs see the same GP and don’t have to waste time repeating their details from scratch at every appointment.”He told the BBC’s Sunday with Laura Kuenssberg programme 8,000 more GPs would be needed to deliver the scheme, which would take “at least four years” and an extra £1bn each year to implement. However, he argued it would save the NHS money in the long term as people would not need to go into hospital so often. Under the current system a patient’s named GP has overall responsibility for the care provided by the surgery. However, people are still able to see any doctor who is available. Minister for public health Andrea Leadsom said: “Just like the Labour Party, the Liberal Democrats can’t say how they will pay for their NHS promises because they don’t have a plan and would take us back to square one.” She said the government was “sticking to the plan to deliver the very best care for patients”, including through their scheme to increase the number of GP training places by 50%. Labour has also promised to cut red tape so patients can see the same GP each appointment if they choose, with shadow health secretary Wes Streeting saying GP practices would be provided with incentives to offer patients continuity of care.Mr Streeting said: “Labour will train thousands more GPs a year so patients can easily book an appointment with their regular GP. “We will cut the red tape that ties up their time, to bring back the family doctor.”More on this storyLib Dems promise right to see a GP within a weekPublished4 November 2022Millions wait more than a fortnight to see a GPPublished21 April 2023

Despite an arsenal of drugs, many Americans are still unaware of their infections until it’s too late. A Biden initiative languishes without Congressional approval.In the 10 years since the drugmaker Gilead debuted a revolutionary treatment for hepatitis C, a wave of new therapies have been used to cure millions of people around the world of the blood-borne virus.Today, 15 countries, including Egypt, Canada and Australia, are on track to eliminate hepatitis C during this decade, according to the Center for Disease Analysis Foundation, a nonprofit. Each has pursued a dogged national screening and treatment campaign.But the arsenal of drugs, which have generated tens of billions of dollars for pharmaceutical companies, has not brought the United States any closer to eradicating the disease.Spread through the blood including IV drug use, hepatitis C causes liver inflammation, though people may not display symptoms for years. Only a fraction of Americans with the virus are aware of the infection, even as many develop the fatal disease.A course of medications lasting eight to 12 weeks is straightforward. But the most at-risk, including those who are incarcerated, uninsured or homeless, have difficulty navigating the American health system to get treatment.Of those diagnosed in the United States since 2013, just 34 percent have been cured, according to a recent analysis by the Centers for Disease Control and Prevention.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

The early results suggest that pasteurization is killing the H5N1 virus in milk, something that regulators were not certain of.Federal regulators on Friday said that they had not yet discovered live bird flu virus in the first batch of retail milk samples they tested, a reassuring indication that the milk on store shelves remains safe despite an outbreak of the virus among diary cows.In an online update, the Food and Drug Administration said an initial set of tests looking for live virus, not just genetic fragments, suggested that the pasteurization process was effectively neutralizing the pathogen.“These results reaffirm our assessment that the commercial milk supply is safe,” the F.D.A. wrote in the update, adding that the testing efforts were ongoing.Officials also tested infant and toddler formula, which incorporate powdered dairy, and did not find the virus, the agency wrote.The F.D.A. embarked on a national survey of milk samples shortly after an outbreak of the bird flu virus, called H5N1, was discovered among dairy cows. Government scientists have been testing 297 samples of retail dairy products from 38 states, a swath of the country that covers regions far beyond the nine states known to have infected herds.The first type of testing regulators conducted, a form of polymerase chain reaction, or PCR, is relatively speedy, but it picks up only genetic traces of the virus and does not tell researchers whether the live pathogen is present.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Rates of breast cancer in women under the age of 50 are rising in Canada according to a study which showed an increase in breast cancer diagnoses among females in their Twenties, Thirties, and Forties.
Led by Dr. Jean Seely, this study published in the Canadian Association of Radiologists Journal reviewed breast cancer cases over 35 years to shed light on trends in breast cancer detection in Canada.
“Breast cancer in younger women tends to be diagnosed at later stages and is often more aggressive,” said Dr. Seely, Head of Breast Imaging at The Ottawa Hospital and Professor in the Department of Radiology at the University of Ottawa. “It’s alarming to see rising rates among women in their Twenties and Thirties because they are not regularly screened for breast cancer.”
Risk increases with age
Using data from the National Cancer Incidence Reporting System (1984-1991) and the Canadian Cancer Registry (1992-2019) at Statistics Canada, the research team, which included Larry Ellison from Statistics Canada and Dr. Anna Wilkinson, an Associate Professor in the Faculty of Medicine, looked at all women aged 20 to 54 who were diagnosed with breast cancer.
Their findings included: For women in their Twenties, there were 3.9 cases per 100,000 people between 1984 and 1988, compared to 5.7 cases per 100,000 between 2015 and 2019 for a 45.5% increase. For women in their Thirties, there were 37.7 cases per 100,000 people between 1984 and 1988, compared to 42.4 cases per 100,000 between 2015 and 2019 for a 12.5% increase. For women in their Forties, there were 127.8 cases per 100,000 people between 1984 and 1988, compared to 139.4 cases per 100,000 between 2015 and 2019 for a 9.1% increase.The study’s results show the importance of targeting younger women in breast cancer awareness campaigns and screening programs. Most public health efforts focus on women over 50, but these findings suggest that younger women are increasingly at risk and may benefit from earlier and more frequent screenings.

Personal experience
Chelsea Bland is one of those women.
Hearing about a death from breast cancer at age 33 led Chelsea — then 28 — to conduct her own self-examination, where she discovered a lump. This led to screenings which ultimately led to a breast cancer diagnosis and subsequent treatment. While she is two years cancer free, she remains on hormone therapy today. The entire experience led Chelsea to help establish a local group that provides peer support for younger women — the average ages range between 28 to 40.
“I hope that by bringing awareness to this study it makes people think twice about saying that being in your twenties, thirties and forties is too young to have breast cancer. In my support group, I have heard the same story over and over again,” Chelsea says. “Young women are not being taken seriously after they find a lump because they are told they are too young for breast cancer. This has ultimately led to delays in being diagnosed and being diagnosed at a more advanced stage. We are not too young for this and this is happening to women who do not have any high-risk genetic markers for breast cancer, myself included.”
Improving awareness
The investigators say more research is needed to understand the root cause of rising breast cancer rates among younger women, information that could be used to develop targeted intervention strategies.
“We’re calling for increased awareness among health-care professionals and the public regarding the rising incidence of breast cancer in younger women,” said Dr. Seely, who alongside Dr. Wilkinson have long documented the benefits of early detection with screening for women in their forties. “We need to adapt our strategies and policies to reflect these changing trends, ensuring that all women, regardless of age, have access to the information and resources they need to detect and combat this disease.”

The case of a Florida bottlenose dolphin found with highly pathogenic avian influenza virus, or HPAIV — a discovery made by University of Florida researchers in collaboration with multiple other agencies and one of the first reports of a constantly growing list of mammals affected by this virus — has been published in Communications Biology.
The report documents the discovery, the first finding of HPAIV in a cetacean in North America, from the initial response by UF’s Marine Animal Rescue team to a report of a distressed dolphin in Dixie County, Florida, to the subsequent identification of the virus from brain and tissue samples obtained in a postmortem examination.
Analyses initially performed at UF’s zoological medicine diagnostic laboratory ruled out the presence of other potential agents at play in the dolphin’s disease, with the Bronson Animal Disease Diagnostic Laboratory in Kissimmee, Florida, verifying the presence of HPAI virus in both the lung and brain.
Those results were confirmed by the National Veterinary Services Laboratory in Ames, Iowa, which characterized the virus subtype and pathotype. The virus was confirmed to be HPAI A (H5N1) virus of HA clade 2.3.4.4b. Subsequent tissue analysis was performed at the Biosafety Level 3 enhanced laboratory at St. Jude Children’s Research Hospital in Memphis.
Allison Murawski, D.V.M., a former intern with UF’s aquatic animal medicine program, was first author on the study and developed a case report on the dolphin as part of her research project. She traveled to Memphis and worked closely with Richard Webby, Ph.D., who directs the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds at St. Jude’s and served as corresponding author on the paper
Webby’s laboratory investigates avian influenza cases in many species and was key in determining where the virus may have originated, what unique RNA characteristics or mutations were present that could suggest its ability to infect other mammals, and how the virus could be tracked from this source.
The researchers sequenced the genomes from local birds and looked at viruses isolated from Northeast seal populations.
“We still don’t know where the dolphin got the virus and more research needs to be done,” Webby said.
“This investigation was an important step in understanding this virus and is a great example where happenstance joins with curiosity, having to answer the ‘why’ and then seeing how the multiple groups and expertise took this to a fantastic representation of collaborative excellence,” said Mike Walsh, D.V.M., an associate professor of aquatic animal health, who served as Murawski’s faculty mentor.

A new imaging technique developed by engineers at Washington University in St. Louis can give scientists a much closer look at fibril assemblies, stacks of peptides like amyloid beta, most notably associated with Alzheimer’s disease.
These cross-β fibril assemblies are also useful building blocks within designer biomaterials for medical applications, but their resemblance to their amyloid beta cousins, whose tangles are a symptom of neurodegenerative disease, is concerning. Researchers want to learn how different sequences of these peptides are linked to their varying toxicity and function, for both naturally occurring peptides and their synthetic engineered cousins.
Now, scientists can get a close enough look at fibril assemblies to see there are notable differences in how synthetic peptides stack compared with amyloid beta. These results stem from a fruitful collaboration between lead author Matthew Lew, associate professor in the Preston M. Green Department of Electrical & Systems Engineering, and Jai Rudra, associate professor of biomedical engineering, in WashU’s McKelvey School of Engineering.
“We engineer microscopes to enable better nanoscale measurements so that the science can move forward,” Lew said.
In a paper published in ACS Nano, Lew and colleagues outline how they used the Nile red chemical probe to light up cross-β fibrils. Their technique called single-molecule orientation-localization microscopy (SMOLM) uses the flashes of light from Nile red to visualize the fiber structures formed by synthetic peptides and by amyloid beta.
The bottom line: these assemblies are much more complicated and heterogenous than anticipated. But that’s good news, because it means there’s more than one way to safely stack your proteins. With better measurements and images of fibril assemblies, bioengineers can better understand the rules that dictate how protein grammar affects toxicity and biological function, leading to more effective and less toxic therapeutics.
First, scientists need to see the difference between them, something very challenging because of the tiny scale of these assemblies.

“The helical twist of these fibers is impossible to discern using an optical microscope, or even some super-resolution microscopes, because these things are just too small,” Lew said.
With high-dimensional imaging technology developed in Lew’s lab the past couple years, they are able to see the differences.
A typical fluorescence microscope uses florescent molecules as light bulbs to highlight certain aspects of a biological target. In the case of this work, they used one of those probes, Nile red, as a sensor for what was around it. As Nile red randomly explores its environment and collides with the fibrils, it emits flashes of light that they can measure to determine where the fluorescent probe is and its orientation. From that data, they can piece together the full picture of engineered fibrils that stack very differently from the natural ones like amyloid beta.
Their image of these fibril assemblies made the cover of the ACS Nano and was put together by first author Weiyan Zhou, who color-coded the image based on where the Nile reds were pointing. The resulting image is a blueish, red flowing assembly of peptides that looks like a river valley.
They plan to continue to develop techniques like SMOLM to open new avenues of studying biological structures and processes at the nanoscale.
“We are seeing things you can’t see with existing technology,” Lew said.