Publisher Health

The spongelike structure of metal organic frameworks (MOFs) allows these polymers to possibly carry and deliver a range of therapeutic compounds. Now, researchers reporting in ACS Applied Bio Materials treated a chromium-containing MOF with a dose of acetic acid, more concentrated than in vinegar, to expand its pore size and surface area. The puffed-up MOFs held more ibuprofen or chemotherapy drug compared to the original version and had improved performance as a potential drug-delivery vehicle.
Taking medications by mouth is a convenient way to administer pharmaceuticals. However, this method sometimes involves ingesting several pills per day, or requires large pills that can be difficult to swallow. So, researchers are investigating how to use MOFs for drug delivery to minimize dosing frequency and maximize treatment efficiency. By customizing the polymers’ pore sizes and structures, scientists have created nanoscale vehicles that may offer more controlled and targeted drug release. However, to carry and deliver even more drug molecules, the pores would need to expand further than current versions can. A research team led by Fateme Rezaei at the University of Miami wanted to optimize an existing MOF and improve the polymer’s delivery of two common therapeutics of different molecular sizes: the anti-inflammatory drug ibuprofen and a smaller compound 5-fluorouracil, a chemotherapy drug used to treat cancer.
They started with an established method to synthesize a biocompatible chromium-containing MOF and added a step with an acetic acid rinse. The acid caused the polymer’s pores to expand from about 2.5 nanometers (nm) to 5 nm wide. In laboratory experiments to characterize the MOF’s drug-loading capability, the researchers observed that the puffed-up version took in more ibuprofen and 5-fluorouracil molecules than the chromium-containing framework with standard-sized pores. Then, in drug-delivery experiments, they loaded the pore-expanded and standard MOFs with either ibuprofen or 5-flurouracil and measured how quickly the drugs passed into a saline solution. Rezaei and colleagues found that the new frameworks released both drugs substantially faster than the original ones. The researchers attributed the higher drug loading and release rates to the larger pores and surface area of the expanded framework, which provides larger “doors” for the drug molecules to enter and exit through.
Simple changes such as these could maximize the effectiveness of MOFs in future drug-delivery applications, the researchers say. As a next step, they plan to determine how slow and progressive drug release within specified time frames can be achieved by modifying MOF pore structure.
The authors acknowledge funding from the U.S. National Science Foundation.

Dozens of people, including babies, were sickened, according to a C.D.C. study that highlighted the risks of snuggling with the strikingly scaly lizards, many of which carry salmonella bacteria in their gut.The outbreak of a rare strain of salmonella that sickened scores of people, including several infants, across the United States and Canada, has been linked to pet bearded dragons, some most likely obtained from the same breeder in Southeast Asia, according to a study published by the Centers for Disease Control and Prevention.The outbreak covered in the study occurred in 2021 and 2022, but salmonella infections associated with bearded dragons have become increasingly common in recent years, mirroring the rising popularity of the goofy, scaly lizards as household pets.Last year, a salmonella outbreak in 20 states affected nearly three dozen people, 10 of whom were hospitalized, according to the C.D.C.No deaths were reported.Bearded dragons, scientifically known as Pogona, are native to Australia, but most of those sold to pet owners are bred in captivity. The banana-size lizards have won the hearts of pet enthusiasts across the world. Not only are they captivating to observe, but bearded dragons also can make engaging pets when provided with proper care.Judging from the many social media accounts that document their adventures, pet bearded dragons spend a fair amount of time frolicking with their owners, wearing adorable outfits and scampering around living rooms and kitchens as if they were dogs.“They are the golden retriever of the reptile world in terms of ease of handling,” said Dr. La’Toya Latney, president of the Association of Reptile and Amphibian Veterinarians and the owner of several pet reptiles. (Unlike dogs, however, bearded dragons are not easy to potty train.)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? 

Published31 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesVisits to the NHS melanoma skin cancer information page soared after the Duchess of York announced she’d been diagnosed with malignant melanoma.There were a total of 13,662 visits in 48 hours – equivalent to one visit every 13 seconds, NHS England says.Melanoma is a type of skin cancer that can spread to other areas of the body.The main cause is ultraviolet light, which comes from the sun and is used in sunbeds – the NHS website provides advice on how to spot it.The Duchess, Sarah Ferguson, was diagnosed with breast cancer in the summer, and after having several moles removed and analysed while having reconstructive surgery, she discovered she also had a form of skin cancer.”I have been taking some time to myself as I have been diagnosed with malignant melanoma, a form of skin cancer,” she said on Instagram on Monday.There are normally around 1,624 visit to the skin cancer NHS web pages in an average 48 hours, but there were eight times that number in the two days after the duchess’s announcement.Professor Peter Johnson, NHS national clinical director for cancer, said: “Skin cancers can come in many different shapes and sizes, and they can be different for everyone. “It’s important to take notice of any changes on your own body and to contact your GP practice to be checked if something doesn’t seem right.”There is a drive to detect and treat cancers at an early stage because that gives people the best chance of successful treatment.Image source, Getty ImagesWhat are the main symptoms of melanoma skin cancer?a mole with an uneven shape or edgesa mole with a mix of coloursa large molea new mole or one that changes size, shape or colour Moles can appear anywhere on the body but are more common in areas exposed to the sun.The NHS website advice is to check your skin for any unusual changes, and see your GP if you notice any. You should use a mirror or ask a partner or friend to check any areas you cannot see.There is more information on what signs to look out for on the Cancer Research UK (CRUC) website with pictures of abnormal moles.CRUK says around 16,700 people are diagnosed with melanoma in the UK each year. That number has gone up over the last few decades, making melanoma the fifth most common cancer in the UK.The Duchess of York is the third royal to announce a medical procedure this week.King Charles announced he was going to be treated for an enlarged prostate last week and is currently in hospital for the procedure. There was a surge in searches for his condition on the NHS website too.The Princess of Wales is also in hospital in London after having planned abdominal surgery.More on this storySearches for enlarged prostate surge, says NHSPublished18 JanuaryDuchess of York ‘shock’ at skin cancer diagnosisPublished4 days agoKing Charles to be treated for benign prostate conditionPublished17 JanuaryPrincess of Wales in hospital after abdominal surgeryPublished17 JanuaryRelated Internet LinksMelanoma skin cancer – NHSBenign prostate enlargement – NHSThe BBC is not responsible for the content of external sites.

Distracted driving is a worsening problem, safety experts say. Yet there is still no definitive database of the number of crashes or fatalities caused by it.Cellphones can track what we say and write, where we go, what we buy and what we search on the internet. But they still aren’t being used to track one of the biggest public health threats: crashes caused by drivers distracted by the phones.More than a decade after federal and state governments seized on the dangers that cellphone use while driving posed and began enacting laws to stop it, there remains no definitive database of the number of crashes or fatalities caused by cellphone distraction. Safety experts say that current estimates most likely understate a worsening problem.The absence of clear data comes as collisions are rising. Car crashes recorded by the police rose 16 percent from 2020 to 2021, to 16,700 a day from 14,400 a day, according to the National Highway Traffic Safety Administration, or N.H.T.S.A. In 2021, nearly 43,000 Americans died in crashes, a 16-year high.In 2021, only 377 fatal wrecks — just under 1 percent — were reported as having involved a cellphone-distracted driver, according to the traffic agency. About 8 percent of the 2.5 million nonfatal crashes that year involved a cellphone, according to the highway agency’s data.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? 

Published57 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, ReutersBy Sean CoughlanRoyal correspondentKing Charles has been admitted to hospital for treatment for an enlarged prostate, says Buckingham Palace.The procedure is being carried out at the London Clinic private hospital, where Catherine, the Princess of Wales had surgery last week.It’s understood the King visited his daughter-in-law in the hospital on Friday morning, ahead of his own scheduled treatment.The King is expected to spend at least one night at the hospital.Queen Camilla was seen with the monarch when he arrived at the hospital in Marylebone in central London.King to get prostate treatment and Kate in hospitalEnlarged prostate: Explaining the King’s conditionSarah Ferguson’s shock at skin cancer diagnosisKing Charles had made his health problem public as a way of sending a message to other men to get their prostates checked.Following the disclosure, the NHS website saw a surge in searches about enlarged prostates, an interest welcomed by doctors and charities.A statement from Buckingham Palace said the King was “delighted to learn that his diagnosis is having a positive impact on public health awareness”.He also thanked those who had “sent their good wishes”.Image source, PA MediaThe plan for King Charles, aged 75, to have “corrective procedure” for his enlarged prostate was revealed by the palace last week. He travelled on Thursday from Sandringham to London to have the operation.A benign prostate problem, which is non-cancerous, is common in older men, according to the NHS.Around one in three men over the age of 50 will have some symptoms of an enlarged prostate, which is a gland that sits just below the bladder.The medical treatment is not significant enough to require any constitutional changes for the King’s role as head of state. There won’t be a need for “counsellors of state” who can stand in when a monarch is seriously ill.A spokeswoman for Prime Minister Rishi Sunak said he had sent best wishes to the King for a “speedy recovery”.The King is being treated in the same hospital where his daughter-in-law Catherine had “abdominal surgery” last week.Image source, EPAWhen she leaves the hospital it is expected that she will spend several months recuperating at home in Windsor. It means the princess will not be taking part in any official duties until after Easter.There was a third royal health story this week, when it was revealed that Sarah Ferguson, the Duchess of York, had been diagnosed with malignant melanoma, a form of skin cancer.It had been discovered during treatment for her breast cancer, which had been diagnosed last summer.”Naturally another cancer diagnosis has been a shock, but I’m in good spirits and grateful for the many messages of love and support,” said the duchess, who was formerly married to Prince Andrew.A spokesman for the duchess said she will have further investigations to ensure the melanoma has been caught in the early stages.More on this storySearches for enlarged prostate surge, says NHSPublished18 JanuaryKate in hospital as King to get prostate treatmentPublished17 JanuaryDuchess of York ‘shock’ at skin cancer diagnosisPublished4 days ago

Published2 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Nottinghamshire PoliceBy Rob SissonsBBC News, NottinghamNHS England is to order a major investigation into triple killer Valdo Calocane’s contact with mental health services, stretching back four years.The 32-year-old fatally stabbed students Barnaby Webber and Grace O’Malley-Kumar, before killing school caretaker Ian Coates last June.A court heard he had been diagnosed with paranoid schizophrenia.The Independent Mental Health Homicide Review will examine what can be learned from the case.On Thursday, Calocane was sentenced to a hospital order, after pleading guilty to three counts of manslaughter on the basis of diminished responsibility, and three counts of attempted murder.It has since been confirmed that the attorney general’s office has received a referral arguing the sentence was unduly lenient.Among the questions the NHS England investigation is likely to examine is whether the killings could have been predicted or prevented. At Calocane’s sentencing hearing, it was revealed the former University of Nottingham student believed MI5 was spying on him.His mental illness began in 2019 and he had been detained under the Mental Health Act at a psychiatric unit in Nottingham four times since May 2020.On each occasion, he was discharged – the final time in February 2022, more than a year before the killings.He was prescribed anti-psychotic medication but stopped taking it, which the prosecution said led to a further decline in his mental health.What is known about Valdo Calocane?Families’ anger as triple killer gets hospital orderPolice ‘should have done more’ to arrest killerFamilies of Calocane’s victims have questioned the care received by the killer in the years leading up to the attacks.Grace O’Malley-Kumar’s father, Dr Sanjoy Kumar, said: “While we have never questioned this man’s diagnosis, the lack of toxicology, contemporaneous mental health assessment, as well as missed opportunities to divert his lethal path will forever play on our minds and this requires further review.”We will look for answers regarding missed opportunities to intervene and prevent this horrendous crime.”Nottinghamshire Healthcare NHS Foundation Trust, which runs mental health services in the county, said in a statement it had “robustly” reviewed its interactions with Calocane.Chief executive Ifti Majid said: “It is important to remember that this person has been convicted of a crime of the most serious kind and there are many people who live with severe mental health issues who do not offend and are supported to live well in their community. “We always aim to care for people in the least restrictive way and to support people to live well in their own homes and society.”If a patient no longer engages with our services and support and they do not meet criteria to be detained under the Mental Health Act, they are discharged back to the care of their GP and can be referred back into our services at any time.”The exact terms of reference of the independent review and the panel that will lead it have yet to be appointed.It is expected it will take many months to complete. Dr Mike Harris, a consultant psychiatrist and former director of Rampton high-security hospital in Nottinghamshire, said examining whether the attacks could have been prevented would be a “very difficult question”.He said: “Essentially it goes back to the observation when he was admitted to hospital nearly a year and a half earlier.”Was there anything in his presentation at that time that would have given any clue to the fact that he might become violent in the future?”It could be there were reasons to follow him up and the follow-up failed for some reason, and in a way that is the most important thing an inquiry can look at.”Did he get better during his admission in 2022 and when he had that, did they arrange appropriate follow-up and did that follow-up happen?”Follow BBC East Midlands on Facebook, on X, or on Instagram. Send your story ideas to eastmidsnews@bbc.co.uk.More on this storyNottingham killer is evil person, says victim’s sonPublished1 day agoPolice ‘should have done more’ to arrest killerPublished1 day agoJail all people who carry knives, says Grace’s mumPublished1 day agoRelated Internet LinksNHS EnglandNottinghamshire Healthcare NHS Foundation TrustThe BBC is not responsible for the content of external sites.

Published3 hours agoShareclose panelShare pageCopy linkAbout sharingBy Rebecca CurranBBC Scotland reporterParents are being urged to heed advice on co-sleeping with babies after new infant death figures were released. BBC News has learned that more than a quarter of infant deaths investigated in Scotland last year involved co-sleeping. The NHS no longer tells parents never to bedshare with their babies but focuses advice on doing so more safely. The solicitor general said the figures suggested some babies were dying in “high-risk” co-sleeping situations. Why Scottish babies are given boxes to sleep inThe Crown Office and Procurator Fiscal Service (COPFS) has for the first time tracked the number of babies who died while co-sleeping with parents, following concerns identified as a result of its investigations.During 2023 it received reports of 74 deaths of babies under the age of 18 months. Of those, it identified 19 babies who died while co-sleeping. In a number of cases the parent or carer had consumed alcohol or drugs. NHS Scotland no longer urges parents never to bedshare with babies, accepting that some parents will do so, but it offers advice on making it safer. It says babies should be placed on their backs, in smoke free-spaces, on firm mattresses with pillows and bedding cleared out of the way to prevent suffocation or overheating.Parents are still told they should not share a bed with their baby if they smoke, have taken alcohol, drugs or medicines that cause drowsiness or if the infant is underweight. They are also told never to co-sleep in armchairs or on sofas. One mother whose baby died after they both fell asleep has shared her story with BBC News in the hope of raising awareness.Dawn Fernand, 33, from Forfar, lost her daughter Fern in November 2014 when she was seven weeks old. Fern had slept in a moses basket during the night but they fell asleep together after an early morning feed. “Then when I woke up, I realised that she wasn’t breathing,” she said. “So at that point, absolute panic set in, an ambulance was called and her dad started CPR straight away but of course it was too late.”Dawn described it as “the biggest rollercoaster I have and will ever go through in my life”.”You are in shock. You are numb. I remember my entire chest, it literally feels like you are getting torn apart.”I lost part of me, and you physically feel the pain of losing that part of you. I will grieve forever. “There were no alcohol or drugs involved in Fern’s death. Tests later revealed she had stopped breathing several times during her life, so co-sleeping may not have been to blame. But Dawn said she still wanted to warn parents about the risks, to prevent another family going through what she had. She said: “With the guidelines recently changing, I don’t think it is clear enough anymore that bedsharing is a risk. Whether you don’t take alcohol or don’t take drugs, it is still a risk to bedshare. “I know how hard it is to raise babies. I know it’s exhausting and I know sometimes all you can do is co-sleep. “But please be aware that there is a risk while doing it. There are ways to make it as safe as possible, but there is still a risk. So I would always advise parents to put their baby asleep on their back, alone in their cot.”Solicitor general, Ruth Charteris KC, said she offered her condolences to anyone who had suffered what was “without doubt one of the most devastating tragedies that a family could experience”. Preventable deathsShe said that overall, safer sleep advice had worked to save the lives of thousands of babies but she was concerned by the findings which showed unsafe co-sleeping was still happening.”I can understand the challenges of getting enough sleep as a family, but expert advice should be followed,” she said.”The evidence of the cases reported to the procurator fiscal shows that, tragically, babies can and do die in high-risk co-sleeping situations.” She added: “It is my sincere hope that by drawing attention to our concerns, prompted by the outcome of our investigations, that the number of baby deaths in which co-sleeping was a preventable factor, can be even further reduced through open conversations about safer sleeping.”Lynsey Kidd, executive director at the Scottish Cot Death Trust, said she was concerned by the figures. She said: “The evidence tells us that for the first six months the safest place for baby to sleep is in a flat, clear, separate space such as a cot, a moses basket or a a crib, in the parents’ room.”So no loose bedding, no toys, no bumpers. In the absence of any other risk factors that is still the safest space for a baby.”We are concerned as a charity because we support many of these families, and whilst we talk about figures, we see the absolute devastation for families across Scotland who are living with the loss of their baby.”The Scottish government said it did not yet know the causes of deaths for the babies that COPFS had been notified of.A spokesperson added: “We are very grateful to the many charities that provide vital support and information to families at this very difficult time of their lives. We know that charities will be available to support families who require this as a result of the solicitor general’s statement.”If you’re affected by the issues in this report, you can find support from BBC Action Line or information from the Scottish Cot Death Trust.Are you affected by the issues raised in this story? Share your experiences by emailing haveyoursay@bbc.co.uk.Please include a contact number if you are willing to speak to a BBC journalist. You can also get in touch in the following ways:WhatsApp: +44 7756 165803Tweet: @BBC_HaveYourSayUpload pictures or videoPlease read our terms & conditions and privacy policy

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A single dose of the typhoid conjugate vaccine, Typbar TCV®, provides lasting efficacy in preventing typhoid fever in children ages 9 months to 12 years old, according to a new study conducted by researchers at University of Maryland School of Medicine’s (UMSOM) Center for Vaccine Development and Global Health (CVD) and led by in-country partners at the Malawi-Liverpool Wellcome Trust (MLW) Clinical Research Programme.
Results from the phase 3 clinical study were published today in The Lancet.
The research team enrolled more than 28,000 healthy children in Malawi and randomly assigned about half the group to receive the TCV and the other half to receive a meningococcal capsular group A conjugate (MenA) control vaccine. During the more than four years of follow-up, 24 children in the TCV group and 110 in the MenA group developed typhoid fever, which was confirmed via blood culture. That resulted in an efficacy of 78.3 percent in the TCV group, with one case of typhoid prevented for every 163 children vaccinated. TCV was effective in all age groups and over the study period — which ended in 2022 — vaccine efficacy remained strong, decreasing by only 1.3 percent per year.
Typhoid fever causes more than 9 million illnesses and at least 110,000 deaths worldwide every year, mostly in sub-Saharan Africa and southeast Asia. It is a contagious bacterial infection that occurs from consuming contaminated food or beverages. Symptoms include nausea, fever, and abdominal pain that, if left untreated, can be deadly.
“These findings have significant implications for identification of the contribution of TCVs in the control and potential elimination of typhoid fever in endemic settings,” wrote the authors of a commentary published in The Lancet alongside the study.
In May 2023, the Malawi government launched a national rollout of the TCV in children under 15 years. Going forward, all children in Malawi will receive TCV at nine months of age as part of the routine immunization schedule.
“The newly published study supports the long-lasting impacts of a single shot of TCV, even in the youngest children, and offers hope of preventing typhoid in the most vulnerable children,” said Kathleen Neuzil, MD, MPH, CVD Director, the Myron M. Levine, MD, DTPH, Professor in Vaccinology at UMSOM and coauthor of the current study. “We could not have had a better partner in this endeavor than MLW, whose long-standing excellence in typhoid research and strong surveillance infrastructure made this study possible.”
“The CVD’s outstanding record of generating data to accelerate public health decisions continues with this landmark study,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “The research could not come at a more critical time when Malawi and other African countries are struggling with climate change, extreme weather events and increased urbanization patterns, which are likely to contribute to increases in enteric diseases, including typhoid.”
TyVAC is funded by the Bill & Melinda Gates Foundation. Typbar TCV® is licensed by Bharat Biotech International Limited, Hyderabad, India.

Witnesses to anti-social behaviour must speak up to support the lone voices of people who confront it to reduce the risk of such behaviour becoming tolerated in society, according to research from the Universities of Bath, Groningen and Western Australia.
Three studies into the impact of bystander conduct showed that when bystanders step in to support someone who is calling out mistreatment or harmful behaviour it sends a strong message to onlookers that this behaviour is unacceptable, helping to prevent a gradual erosion of social norms.
Conversely, staying silent, or changing the subject to avoid awkwardness, can be interpreted by others as a lack of agreement and undermines the efforts of the confronter.
The research shows bystander actions are pivotal in helping or hindering efforts to address anti-social behaviour.
“If something anti-social happens we look to someone to step in and say something,” says lead researcher Anna Tirion. “It’s tempting to think ‘someone else has got this’ and we don’t need to get involved, but what we’ve been ignoring is that the initial confrontation is not the end of the interaction. If other bystanders stay out of it, it’s not without consequences.
“If no one says anything to support the confrontation, people start to think the norm wasn’t that strong. It chips away at pro-social norms that protect being kind and helpful to others, and not causing harm. Over time people start to think a particular (antisocial) behaviour doesn’t matter,” said Tirion.
The researchers hope that the findings will make a positive contribution to bystander training. They hope that future studies will also look at the role of bystanders in whistleblowing scenarios and other contexts, such as when the people involved are all strangers.

The research was conducted during Tirion’s undergraduate psychology studies at Bath, on a placement year at the University of Groningen in the Netherlands.
The studies investigated the effect of bystander responses to social confrontation in the context of Covid-19 social distancing rules, which were in place in most European countries in 2020-2021.
Participants were shown various scenarios where someone confronted a social distancing rule-breaker (admitting to hosting/ attending parties during lockdown) to investigate the effect of different bystander reactions (support, silence, or changing the subject) on how strong participants found the norm of following the rules.
The researchers also measured to what extent the participants thought the bystanders agreed with the confronter based on their reaction. When the confronter was left without support, participants concluded that the bystanders did not strongly agree, leading them to think the norm to socially distance was weak.
Despite the specific Covid context the researchers say that understanding the mechanisms of this behaviour makes it widely applicable to social confrontations in the workplace, on public transport, and in society at large.
“How bystanders can lend their support depends a bit on the situation,” said Tirion. “If your face is visible to everyone, like on the Zoom call we simulated in one of our studies, simply nodding might be enough to send that supportive signal. Otherwise, a verbal expression of support like ‘Yeah, you’re/they’re right’ should do it.
“If you’re physically some distance away from the confrontation, you might want to go stand next to the confronter before you say something so your whole body language expresses that support — if you feel safe to do so.”
Co-author Dr Annayah Prosser, from the University of Bath’s School of Management, said: “There is a personal cost for people to go against the norm, to cause tension and friction. Even if people find someone’s behaviour unacceptable there is a social norm against speaking up. Causing friction is uncomfortable and this can hold people back.”
People may also be reluctant to step in for fear of overkill, but the researchers say this is far from the current reality. “People’s intuitive response can be that it will be a ‘pile-on’ but this is not a problem currently,” said Dr Prosser. “People are taking a lot of social risk to intervene and going unsupported. We need to make sure intervention against anti-social behaviour is supported by bystanders, and not just met with silence.”

Around one million individuals worldwide become infected with HIV, the virus that causes AIDS, each year. To replicate and spread the infection, the virus must smuggle its genetic material into the cell nucleus and integrate it into a chromosome. Research teams led by Dirk Görlich at the Max Planck Institute for Multidisciplinary Science and Thomas Schwartz at the Massachusetts Institute of Technology (MIT) have now discovered that its capsid has evolved into a molecular transporter. As such, it can directly breach a crucial barrier, which normally protects the cell nucleus against viral invaders. This way of smuggling keeps the viral genome invisible to anti-viral sensors in the cytoplasm.
Forty years after the human immunodeficiency virus (HIV) was discovered as the cause of AIDS, we have therapies that effectively keep the pathogen under control, but there is still no cure. The virus infects certain immune cells and hijacks their genetic program in order to multiply and replicate its own genetic material. The infected cells then produce the next generation of viruses until they are finally destroyed. The immunodeficiency symptoms of AIDS result from the massive loss of immune cells that normally fight viruses and other pathogens.
To use the host cell’s resources, HIV must smuggle its genetic material through cellular defense lines into the cell nucleus. The nucleus, however, is closely guarded. Its nuclear envelope prevents unwanted proteins or harmful viruses from entering the nucleus and macromolecules from an uncontrolled escape. Yet, selected proteins can pass because the barrier is not hermetically sealed.
Thousands of tiny nuclear pores in the nuclear envelope provide a passageway. They control these transport processes with the help of importins and exportins — molecular transporters that capture cargoes with valid molecular “passcodes” and deliver them through the nuclear pore channel. A ‘smart’ material turns these pores into one of nature’s most efficient sorting and transport machines.
“Smart” sorting in the nuclear pore
This “smart” material, called FG phase, is jelly-like and impenetrable for most macromolecules. It fills and blocks the nuclear pore channel. Importins and exportins, however, can pass through because their surfaces are optimized for sliding through an FG phase.
The cell’s border control in the FG phase happens extremely fast — within milliseconds. Likewise, its transport capacity is enormous: a single nuclear pore can transfer up to 1,000 transporters per second through its channel. Even with such a high traffic density, the barrier of nuclear pores remains intact and keeps suppressing unwanted border crossings. HIV, however, subverts this control.

Smuggled genetic material
“HIV packages its genome into a capsid. Recent evidence suggests that the genome stays inside the capsid until it reaches the nucleus, and thus also when passing the nuclear pore. But there is a size problem,” Thomas Schwartz of MIT explains. The central pore channel is 40 to 60 nanometers wide. The capsid has a width of about 60 nanometers and could just squeeze through the pore. However, a normal cellular cargo would still be covered by a transporter layer that adds at least another ten nanometers. The HIV capsid would then be 70 nanometers wide — too big for a nuclear pore. “Nevertheless, cryo-electron tomography has shown that the HIV capsid gets into the nuclear pore. But how this happens has been so far a mystery in HIV infection,” says Max Planck Director Görlich.
Camouflage as a molecular transporter
Together with Schwartz, he has now discovered how the virus overcomes its size problem, namely by a sophisticated molecular adaptation. “The HIV capsid has evolved into a transporter with an importin-like surface. This way, it can slide through the FG phase of the nuclear pore. The HIV capsid can thus enter the nuclear pore without helping transporters and bypass the protective mechanism that otherwise prevents viruses from invading the cell nucleus,” the biochemist explains.
His team has succeeded in reproducing FG phases in the laboratory. “Under the microscope, FG phases appear as micrometer-sized spheres that completely exclude normal proteins, but virtually suck up the HIV capsid with its enclosed contents,” reports Liran Fu, one of the first authors of the study now published in the journal Nature. “Similarly, the capsid is sucked up into the nuclear pore channel. This happens even after all cellular transporters have been removed.”
In one respect the HIV capsid differs fundamentally from previously studied transporters that pass nuclear pores: It encapsulates its cargo completely and thus conceals its genomic payload from anti-viral sensors in the cytoplasm. Employing this trick, the viral genetic material can be smuggled through the cellular virus defense system without being recognized and destroyed. “This makes it another class of molecular transporters alongside importins and exportins,” Görlich emphasizes.
There are still many unanswered questions, such as where and how the capsid disintegrates to release its contents. However, the observation that the capsid is an importin-like transporter might one day be exploited for better AIDS therapies.