Publisher Health

The secret to protecting your memory may be a staple of a bodybuilder’s diet. RUSH researchers recently discovered that a muscle-building supplement called beta-hydroxy beta-methylbutyrate, also called HMB, may help protect memory, reduce plaques and ultimately help prevent the progression of Alzheimer’s disease.
HMB is not a prescription drug or a steroid, but an over-the-counter supplement that is available in sports and fitness stores. Bodybuilders regularly use HMB to increase exercise-induced gains in muscle size and strength while improving exercise performance. HMB is considered safe even after long-term use, with no known side effects.
“This may be one of the safest and the easiest approaches to halt disease progression and protect memory in Alzheimer’s disease patients,” said Kalipada Pahan, PhD, the Floyd A. Davis, MD, Professor of Neurology and professor of neurological sciences, biochemistry and pharmacology at RUSH Medical College.
Studies in mice with Alzheimer’s disease have shown that HMB successfully reduces plaques and increases factors for neuronal growth to protect learning and memory, according to neurological researchers at RUSH.
“Understanding how the disease works is important to developing effective drugs to protect the brain and stop the progression of Alzheimer’s disease,” Pahan said.
Previous studies indicate that a family of proteins known as neurotrophic factors are drastically decreased in the brains of people with Alzheimer’s disease and have been found to help in survival and function of neurons, which are cells that receive and send messages from the body to the brain and vice versa.
“Our study found that after oral consumption, HMB enters into the brain to increase these beneficial proteins, restore neuronal connections and improve memory and learning in mice with Alzheimer’s-like pathology, such as plaques and tangles,” Pahan said.

Extensive damage occurred at the company’s property in Rocky Mount, and many products used by hospitals appeared to have been affected. This could further exacerbate shortages.A Pfizer facility and several homes sustained major damage when a tornado ripped through a 16-mile strip of Rocky Mount, N.C.By The Associated PressA tornado caused extensive damage to a Pfizer drug manufacturing site in Rocky Mount, N.C., on Wednesday, threatening critical supplies for hospitals across the country.The company estimated that one-fourth of the injectable medications it supplies to U.S. hospitals were made at the Rocky Mount property, including drugs used during surgeries and other procedures to help block pain, keep patients sedated and fight infections.Though the company has yet to disclose the extent of the storm’s impact, video footage of the site and interviews with the Nash County sheriff and with people briefed on the damage indicated that the tornado caused the worst damage at the company’s warehouse.On Thursday, Pfizer declined to comment on the drugs affected or the proportion of its supply destroyed in the tornado, which could be considerable given that a lot of these medications required careful production and handling to ensure sterility.It was also unclear how deeply the destruction would exacerbate existing national drug shortages, which have reached a 10-year high in recent months. Hospitals are on high alert because low-cost generic products manufactured at the site, are already among the most shortage-prone on the market.“From a health care practitioner point of view, I’m just holding my breath,” said Michael Ganio, a senior director at the American Society of Health-System Pharmacists.The tornado ripped through a 16-mile strip of the Rocky Mount area, about 50 miles east of Raleigh, at about 12:30 p.m. on Wednesday. It snapped trees at the base and tossed homes 20 yards from their foundations, according to a summary by the National Weather Service. The tornado reached wind speeds up to 150 miles per hour before it ripped off large pieces of the metal roof of a Pfizer building and flipped big-rig trucks in the parking lot. Sixteen people were injured, but no deaths were reported.Several people said the tornado caused the most damage to a company warehouse; the impact to the manufacturing plant — and its ability to continue producing medicines — is not yet clear, according to Mittal Sutaria, a senior vice president of pharmacy contracts at Vizient, which provides contracting for medications to hospitals.She said Pfizer had teams on-site to assess the damage.Dr. Sutaria, who said Vizient had been in touch with Pfizer, added that the Rocky Mount site made anesthesia products, as well as fentanyl and morphine, which are used in IVs for pain management. It also makes antibiotics administered to fight severe infections, and muscle blockers including succinylcholine, also used in surgery.Keith Stone, the sheriff of Nash County, where Rocky Mount is situated, told local news reporters on Wednesday that much of the Pfizer building was splintered, the roof was crushed and as many as 50,000 pallets of medicine were destroyed.About 100 vehicles were also damaged, including forklift trucks that were strewn across nearby railroad tracks, Sheriff Stone said in an interview on Thursday. “It’s just amazing what can come up so quick and have so much damage and be gone so fast,” he said.Steve Danehy, a spokesman for Pfizer, said on Thursday that the company’s Rocky Mount team was “working very hard to address and assess the situation,” but did not provide any details. The company said its staff survived the tornado without serious injuries.Pfizer is expected to report its findings to the Food and Drug Administration, which tracks shortages.“We are following the situation closely as it evolves and are working with the company to understand the extent of the damage and any potential impact to the nation’s drug supply,” said Chanapa Tantibanchachai, a spokeswoman for the agency.The Rocky Mount facility, established in 1968, employs 4,500 people and has 24 filling lines and 22 packing lines. Though not as large as Pfizer’s manufacturing complex in Kalamazoo, Mich., the North Carolina site spans 1.4 million square feet of manufacturing space. The medicines made at the site are also shipped to Japan, Canada, Brazil and other countries.The specific products made at the Pfizer plant — and the share of the market they comprise — is not typically public information. However, the company sells dozens of injectable items, including I.V. antibiotics, anti-seizure drugs used in brain surgery and even an antidote to coral snake venom.Many Pfizer medicines were already in short supply before the tornado: About 130 products marketed to hospitals were listed as “depleted” and about 100 more were in “limited supply,” according to the company’s list of 660 products.Pfizer has other manufacturing plants in Kansas, New York, Massachusetts and Wisconsin where the company could possibly shift some production to ease any shortages resulting from the Rocky Mount destruction.Soumi Saha, a senior vice president with Premier, a company that provides contracting services for medications to hospitals, said that Pfizer had a strong track record for building in some redundancy so that products were manufactured at more than one site.If the storm damage is limited to the warehouse and does not affect production schedules at the manufacturing plants, that could mitigate potential shortages, she said.Dr. Ganio recalled other drug shortages caused by disasters in production zones.Hurricane Maria struck Puerto Rico in 2017, leaving hospitals scrambling for IV bags. Another occurred last year when a region of China that was hard-hit by Covid had a lapse in producing contrast dye for CT scans and other medical images. And in recent months, doctors have warned that survival rates for some cancer patients are in jeopardy because of a halt in production at a manufacturing plant in India after the F.D.A. cited major quality lapses.Given the worrisome shortages that affect so many lives — and that have resulted in hoarding of certain drugs and bartering among advocates who trade and find scarce drugs for the most desperate — policy experts, lawmakers and federal officials have been discussing solutions in recent weeks.On Thursday, Senate lawmakers passed a pandemic preparedness bill out of a key health committee. It had provisions aimed at stemming shortages and increasing reports by drugmakers to alert the F.D.A. to circumstances that might lead to shortages so the agency could help head them off. The bill would also require a report from the F.D.A. within 90 days of the legislation’s passage on the agency’s ability to deal with shortages and whether it needs more help from lawmakers.Still, the natural occurrence of a tornado provided a stark reminder of the need to better manage shortages.“This reinforces the need for resiliency in our supply chain and a true focus on preparedness, not only for the next pandemic,” Dr. Saha said, “but for any unforeseen circumstance that creates shocks in our supply chain.”

In 2017, the National Institutes of Health (NIH) announced a dramatic reversal in its approach to peanut-allergy prevention, recommending parents expose their infants as young as four months old to peanuts to prevent peanut allergy.
In the five years since, early introduction to peanuts has been gaining traction among U.S. parents and caregivers, but more work must be done to communicate the guidelines more broadly, especially to those with less access to health-related information, reports a new study from Northwestern University and the Ann & Robert H. Lurie Children’s Hospital of Chicago. Among all surveyed parents and caregivers in the U.S., 13% of parents said they’re aware of the guidelines and 48% believed feeding peanuts early prevented peanut allergy, despite knowing about the guidelines or not.
“There was general awareness of ‘If I give these foods early, it will help,’ even if families didn’t know it came from the NIH guidelines,” said Dr. Waheeda Samady, associate professor of pediatrics at Northwestern University Feinberg School of Medicineand director of clinical research at Northwestern’s Center for Food Allergy and Asthma Research. “There’s still a lot of room for growth in terms of educating families and clinicians about these guidelines.”
The study found that having a pediatrician who recommended early peanut introduction was the strongest factor in whether a parent or caregiver was aware of the guidelines.
“This study is taking a look at something still so new to health systems in the U.S.,” said senior author Dr. Ruchi Gupta, director for the Center for Food Allergy and Asthma Research, professor of pediatrics and a pediatrician at Lurie Children’s Hospital. “As a pediatrician, I’m sensitive to the fact that there is a lot to juggle during a four- or six-month appointment. We need to find ways to support pediatricians in their workflows to incorporate the prevention guidelines.”
The study is the first nationwide survey to examine the impact and implementation of the guidelines since their release five years ago. It will be published July 21 in Pediatrics.
The authors said the findings provide an understanding of where American parents land on peanut feeding and where the gaps are. This includes: Access to care barriers and systemic racism, which makes this information less known to non-white, less-educated and lower-income parents Supporting primary care providers to provide this information in a timely way Public health messaging about reactions to peanuts, since this was the main fear reported in the surveyA closer look at the findings:

An interdisciplinary research team from Bochum, Duisburg and Zurich has developed a new approach to construct modular optical sensors which are capable of detecting viruses and bacteria. For this purpose, the researchers used fluorescent carbon nanotubes with a novel type of DNA anchors that act as molecular handles. The anchor structures can be used to conjugate biological recognition units such as antibodies aptamers to the nanotubes. The recognition unit can subsequently interact with bacterial or viral molecules to the nanotubes. These interactions effect the fluorescence of the nanotubes and increase or decrease their brightness.
A team consisting of Professor Sebastian Kruss, Justus Metternich and four co-workers from Ruhr University Bochum (Germany), the Fraunhofer Institute for Microelectronic Circuits and Systems and the ETH Zurich reported their findings in the Journal of the American Chemical Society, published online on 27 June 2023.
Straightforward customisation of carbon nanotube biosensors
The team used tubular nanosensors that were made of carbon and had a diameter of less than one nanometre. When irradiated with visible light, carbon nanotubes emit light in the near-infrared range. Near-infrared light is not visible to the human eye. However, it is perfect for optical applications, because the level of other signals in this range is highly reduced. In earlier studies, Sebastian Kruss’ team had already shown how the fluorescence of nanotubes can be manipulated in order to detect vital biomolecules. Now, the researchers searched for a way to customise the carbon sensors for use with different target molecules in a straightforward manner.
The key to success were DNA structures with so-called guanine quantum defects. This involved linking DNA bases to the nanotube to create a defect in the crystal structure of the nanotube. As a result, the fluorescence of the nanotubes changed at the quantum level. Additionally, the defect acted as a molecular handle that allowed to introduce a detection unit, which can be adapted to the respective target molecule for the purpose of identifying a specific viral or bacterial protein. “Through the attachment of the detection unit to the DNA anchors, the assembly of such a sensor resembles a system of building blocks — except that the individual parts are 100,000 times smaller than a human hair,” outlines Sebastian Kruss.
Sensor identifies different bacterial and viral targets
The group showcased the new sensor concept using the SARS CoV-2 spike protein as an example. To this end, the researchers used aptamers, that bind to the SARS CoV-2 spike protein. “Aptamers are folded DNA or RNA strands. Due to their structure, they can selectively bind to proteins,” explains Justus Metternich. “In the next step, one could transfer the concept to antibodies or other detection units.”
The fluorescent sensors indicated the presence of the SARS-CoV-2 protein with a high degree of reliability. The selectivity of sensors with guanine quantum defects was higher than the selectivity of sensors without such defects. Moreover, the sensors with guanine quantum defects were more stable in solution. “This is an advantage if you think about measurements beyond simple aqueous solutions. For diagnostic applications, we have to measure in complex environments e.g. with cells, in the blood or in the organism itself,” says Sebastian Kruss, who heads the Functional Interfaces and Biosystems Group at Ruhr University Bochum and is a member of the Ruhr Explores Solvation Cluster of Excellence (RESOLV) and the International Graduate School of Neuroscience.

Researchers from the University of Liverpool have created a biomedical compound that has the potential to stop the spread of breast cancer. A recently published paper details these early findings.
Scientists from the Chemistry and Biochemistry Departments at the University of Liverpool and Nanjing Medical School in China have discovered a possible way to block proteins produced in the body when a patient has cancer and which causes its spread to other parts of the body. This process, called metastasis, is largely responsible for patient deaths.
The major problem hindering the successful treatment of commonly occurring cancers is not the primary tumour which can usually be removed by surgery, but its spread to other organs of the body.
Prof Philip Rudland, Emeritus Professor in the University of Liverpool’s Department of Biochemistry, explained: “As a general rule, cancer that has spread is treated with chemotherapy, but this treatment can rarely be given without severely harming or becoming toxic to the patient. The importance of our work was to identify a specific and important target to attack, without toxic side effects.”
The University’s research team have in the past discovered that specific proteins are involved in the metastatic process; these proteins are different from those involved in the production of the primary tumour. One such example is a protein called ‘S100A4’, and is the protein chosen by the research team to target for the identification of chemical inhibitors of metastasis, using model systems of cells from the highly metastatic and incurable hormone receptor-free breast cancer.
Using these model systems, researchers at the University’s Department of Biochemistry discovered a novel compound that can specifically block the interaction of this metastasis-inducing protein S100A4 with its target inside the cell. Researchers in the Department of Chemistry then synthesised a simpler chemical and connected it to a warhead which stimulates the normal protein degrading machinery of a cell. This compound now works at very low doses to inhibit properties associated with metastasis, an improvement of over 20,000-fold on the original unarmed inhibitor, with virtually no toxic side effects. Moreover, in collaboration with Chinese researchers at Nanjing Medical School, they have shown that this compound inhibits metastasis in similar metastatic tumours in mice, suggesting a potential therapeutic role.
Dr Gemma Nixon, Senior Lecturer in Medicinal Chemistry at the University of Liverpool said: “This is an exciting breakthrough in our research. We now hope to take the next steps, and repeat this study in a large group of animals with similar metastatic cancers so that the efficacy and stability of the compounds can be thoroughly investigated and if necessary improved by further design and syntheses, prior to any clinical trials.”
“Significantly, this particular protein we’re investigating occurs in many different cancers, which could mean this approach may be valid for many other commonly occurring human cancers.”
The project was led by Dr Gemma Nixon and Prof Philip Rudland with Research Associate Dr Thamir Ismail, former PhD student Dr Rachel Crick, and biologists Dr Weiping Yu and Dr Zhenxing Cheng at Southeast University, Nanjing with Prof Guozheng Wang liaising between the two Universities.
Funding support for the project was provided by The Cancer and Polio Research Fund, Medical Research Council, Cancer Research UK, and Engineering and Physical Sciences Research Council.

UK researchers have found that people with longer-term COVID-19 symptoms including brain fog showed reduced performance in tasks testing different mental processes up to two years after infection with the virus.
Researchers from King’s College London looked at whether infection with COVID-19 affected performance in two rounds of online cognitive testing that took place in 2021 and 2022. Data was collected for over 3,000 participants of the COVID Symptom Study Biobank study, across 12 tasks that tested memory, attention, reasoning, processing speed and motor control.
The participants whose test scores were most affected by COVID-19 were those who had experienced symptoms related to the virus for 12 weeks or more. In these people, the effect of COVID-19 on test accuracy was comparable in size to the effect of a 10-year increase in age.
There was no significant improvement in these test scores between the two rounds of testing, which took place nine months apart. By the second round of testing, the average time since participants’ initial COVID-19 infection was almost two years.
Digging deeper into the analysis, the researchers separated participants by whether they felt fully recovered following COVID-19 infection. People who felt fully recovered after COVID-19 infection performed similarly to those who had not had the virus at all. In contrast, participants who did not feel fully recovered after infection had lower task accuracy scores on average.
Lead author Dr Nathan Cheetham, a Senior Postdoctoral Data Scientist at King’s College London said:
“Our findings suggest that, for people who were living with long-term symptoms after having COVID-19, the effects of the coronavirus on mental processes such as the ability to recall words and shapes are still detectable at an average of almost two years since their initial infection.
“However, the result that COVID had no effect on performance in our tests for people who felt fully recovered, even if they’d had symptoms for several months and could be considered as experiencing ‘long COVID’, was good news. This study shows the need to monitor those people whose brain function is most affected by COVID-19, to see how their cognitive symptoms continue to develop and provide support towards recovery.”
Professor Claire Steves, a Professor of Ageing and Health at King’s College London, added:
“We used sensitive tests to measure speed and accuracy across a range of brain challenges. This study shows that some individuals have measurable changes in these tests after COVID-19 going on for nearly two years. The fact remains that two years on from their first infection, some people don’t feel fully recovered and their lives continue to be impacted by the long-term effects of the coronavirus. We need more work to understand why this is the case and what can be done to help.”

The widespread, pathogenic microbe Staphylococcus aureus can colonize the skin and mucous membranes throughout the body, particularly the vagina and gastrointestinal tract. A virulent strain of the bacterium produces proteins that trigger toxic shock syndrome (TSS), a disease characterized by the quick onset of fever, a telltale rash, and, without treatment, multi organ failure. In the vagina, TSS is associated with a life-threatening reaction from the immune system.
Probiotics may help prevent the disease before the cytokine cascade ever begins. A study published in the American Society for Microbiology’s journal Microbiology Spectrum reports that strains of 2 bacteria, Lactobacillus acidophilus and Lacticaseibacillus rhamnosus, successfully inhibited the production of the superantigens that cause TSS, in lab experiments. L. acidophilus, in addition, inhibited the growth of the S. aureus strains that produce the problematic proteins.
A combination of the 2 could both prevent growth and inhibit the immune response. “It’s kind of a double whammy against S. aureus,” said microbiologist Patrick Schlievert, Ph.D., at the University of Iowa Carver College of Medicine, in Iowa City. “If any toxin is made, the probiotics still prevent inflammation.”
He noted that adding these probiotics to tampons or other menstrual products could reduce the risk — and global incidence — of TSS associated with menstruation. Such a preventive measure has the potential to benefit millions of vulnerable people, Schlievert said. “We know that 20% of people over age 12 cannot make antibodies and never will make antibodies against toxic shock syndrome,” he said.
Schlievert has been studying TSS — and its prevention — for decades. In the early 1980s, he was the first researcher to identify the toxin that triggers an overreaction of the immune system, and to show how high-absorbency tampons facilitated production of that toxin if S. aureus was present.
The new work, he said, was motivated by observations made during an earlier study. A few years ago, he and his colleagues recruited 205 women to test whether a novel molecular mixture, when added to tampons, would inhibit pathogenic bacteria. That molecule proved effective against E. coli and other pathogens, but the researchers noticed an unexpected consequence.
“Some of the women in the treatment group had this tremendous growth of Lactobacilli,” Schlievert said.

About one in two women are affected by cystitis during her lifetime, and many suffer from recurrent urinary tract infections. Bladder infections are not only painful and potentially dangerous, but they also pose a significant dilemma for physicians. With antibiotic resistance becoming widespread in urinary tract infections and continually increasing, physicians are often forced to blindly prescribe antibiotics without knowing their effectiveness against the pathogen causing the infection. This is because it takes several days to identify a specific pathogen using conventional diagnostics.
Researchers at ETH Zurich, in collaboration with Balgrist University Hospital, have now developed a rapid test that employs the natural viral predators of bacteria, bacteriophages. The researchers also genetically modified the phages to make them more efficient at destroying the pathogenic bacteria.
Fast and reliable diagnosis
Phages are highly specialised viruses. Each species of phage infects only one particular type or strain of bacteria. ETH Zurich scientists from the Food Microbiology research group led by Professor Martin Loessner are now taking advantage of this unique characteristic. The first step was to identify the phages that are effective against the three main types of bacteria implicated in urinary tract infections, namely Escherichia coli, Klebsiella and Enterococci.These natural phages were then modified in such a way that any bacteria they recognize and infect are propelled to produce an easy-to-measure light signal.
Using this method, the researchers were able to reliably detect the pathogenic bacteria directly from a urine sample in less than four hours. In the future, the method could make it possible to prescribe a suitable antibiotic immediately after diagnosis and thus minimize resistance development and improve antibiotic stewardship.
The method also has another advantage: it allows physicians to predict which patients are likely to respond particularly well to a tailored phage therapy, as the strength of the light signal produced in the assay already indicates how efficient the phages are in attacking the bacterium — the more the sample glows, the better the bacterium will respond to the therapy.
Double-action sniper
Phage therapies have been used for over 100 years but fell into oblivion in Western industrialised countries with the discovery of penicillin. In view of increasing antibiotic resistance, they are currently seeing a renaissance. They also have the decisive advantage of attacking only a single target bacterium, much like a sniper.

Errors in installation of child car seats are common, even with seats that have a five-star rating for ease of use, according to a study published in the journal Traffic Injury Prevention. The study found that although the rating system was a suitable indicator of ease of use, with fewer errors detected when parents installed seats that had higher ratings, more efforts are needed to ensure optimal safety for young passengers.
Child restraint systems (CRSs) reduce risk of crash-related injury by 50%-85%, however use errors undermine their benefits. The National Highway Traffic Safety Administration (NHTSA) created the Ease of Use (EOU) rating system to help guide consumers and incentivize manufacturers to improve their products. The EOU rating system assigns one to five stars to four CRS features and overall.
Child passenger safety technicians working in the community and with car seat manufacturers are available to answer questions about installing and using car seats. The NHTSA website provides a resource directory by zip code to help parents connect with a local certified child passenger safety technician who can check if the seat is installed correctly or provide help on installing and using an appropriate car seat.
“New parents often receive training on car seat installation before the baby is born. However, it would be beneficial for them to take advantage of the available resources after the child’s birth as well, especially during the transition from infant carrier to rear-facing car seat, and then again when switching to the seat to face forward,” said lead author Michelle Macy, MD, MS, Emergency Medicine physician at Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine.
Dr. Macy and colleagues analyzed data from Safe Kids Illinois seat check records from 2015 through 2019 and EOU ratings from 2008 to 2020. Errors were most common for seats installed with seat belts (70%) and least common for recline angle (37%).
One of the more common errors that was found around 50% of the time, even with 5-star rated car seats, involved the top tether on forward-facing car seats. The top tether is a strap on the top of the seat that needs to be hooked to an anchor point on the vehicle. Often parents either do not attach the strap or hook it to the wrong location.
“Overall, our study results show that parents can rely on the car seat rating system when choosing an appropriate car seat for their child,” said Dr. Macy. “They just need to be aware that installation and use errors can still occur even with the top-rated car seats. We encourage parents to get help from a certified technician to ensure their child’s safety on the road.”
Dr. Macy holds the Mary Ann & J. Milburn Smith Research Professorship for the Director of Child Health Research. She is the Director of Mary Ann & J. Milburn Smith Child Health Outcomes, Research and Evaluation Center; and Scientific Director of Community, Population Health, and Outcomes at Stanley Manne Children’s Research Institute.
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is a nonprofit organization committed to providing access to exceptional care for every child. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine. Emergency medicine-focused research at Lurie Children’s is conducted through the Grainger Research Program in Pediatric Emergency Medicine.

Researchers at the Francis Crick Institute and UCL have shown that hundreds of proteins and mRNA molecules are found in the wrong place in nerve cells affected by Motor Neuron Disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS).
ALS is a rapidly progressing and devastating condition that causes paralysis by affecting motor neurons, with limited treatment options. Until now, scientists were aware that a few proteins, especially a protein called TDP-43, were found in unexpected locations in ALS nerve cells.
But new research published today in Neuron shows that the problem is much broader. This ‘mislocalisation’ affects many more proteins than first thought, especially those involved in RNA binding. The mislocalisation extends to mRNAs too, molecules that deliver instructions to make proteins from the DNA in the nucleus.
The researchers used stem cells from patients to create motor neurons with ALS-causing mutations in the TARDBP and VCP genes. They then separated the two main compartments of the cell (nucleus and cytoplasm), and analysed all the mRNA and protein within each. They found that in ALS cells, hundreds of mRNAs and proteins were mislocated compared to healthy cells.
They observed proteins and mRNAs relocating from the cell’s nucleus (the ‘control centre’) into the cytoplasm (the ‘body’ of the cell) or vice versa, hinting at potential transport issues within the cell.
The researchers also saw that mislocated mRNAs and proteins interacted more with each other, compared to those in the right place. They speculate that as the mRNAs and proteins mislocalise, they may drag each other with them, creating a domino effect.
Oliver Ziff, Clinician Scientist at the Crick and UCLH, said: “We were surprised to see the extent of the mislocalisation, particularly for mRNAs, as this hasn’t been reported before. The goal now is to find where this problem starts and there are many intriguing possibilities — one being a breakdown in the transport between the nucleus and cytoplasm. This study was an exceptional team effort, and I’m immensely grateful to my colleagues, particularly co-first authors, Drs Jasmine Harley, Yiran Wang, and Jacob Neeves.”
Remarkably, the mislocalisation of proteins and mRNAs was partially improved with a drug called ML240, which blocks the action of the VCP enzyme. Blocking this enzyme also led to other beneficial effects on cell function, such as reducing the level of damage to DNA.