Publisher Health

Researchers from the Babraham Institute, UK, and the German Center for Neurodegenerative Diseases (DZNE) have identified a backup mechanism of protein quality control which prevents the toxic effects of protein aggregation in specific tissues when normal methods of molecular monitoring fail. By understanding how different tissues tackle protein build up, this research could accelerate the identification of ways to protect tissues that are vulnerable to protein build up, possibly tackling both disease-associated protein aggregates and also age-dependent aggregates that accelerate the functional decline of tissues.
Just like factories identifying faulty items coming off the production line, cells use different mechanisms to monitor protein production, folding and accumulation. During ageing some proteins become prone to accumulating due to disrupted protein folding and the decline in the protein quality control mechanisms. Protein clumps called aggregates cause problems for normal functioning of the organism. This increase in protein accumulation is not evenly distributed across the body and some tissues are more likely to accumulate aggregates of certain proteins than others, for example amyloid plaques that build up in the brain during Alzheimer’s disease. What drives the tissue-specific vulnerability or resistance to protein aggregation remains poorly understood.
By studying protein accumulation in the nematode worm C. elegans Dr Della David and her team found that even when the typical protein quality control mechanisms were disrupted, there were lower levels of protein aggregation in the feeding organ of aged worms, the pharynx, compared to the body walls. Their experiments revealed a tissue-specific mechanism they’ve called ‘SAPA: safeguard against protein aggregation’ which kicks in when other protein quality control mechanisms are defective. When activated, this mechanism alleviated proteotoxicity and partially restored pharyngeal function.
“Organisms have a set of control mechanisms found in all tissues that deal with the build-up of defective proteins. In this work we have identified a new tissue-specific control mechanism. This safety mechanism is triggered when conventional control mechanisms are impaired and we’re excited about its discovery because it reveals an extra layer of protection which can be triggered to protect tissues in times of stress, actively stopping protein aggregation and restoring function to the organ” said Dr Della David, group leader in the Signalling research programme at the Babraham Institute.
But how is this specificity achieved? To prevent aggregation specifically in the pharynx,
the safety mechanism relies on a specific and understudied pathway made up of the cells rubbish disposal system called macroautophagy-independent lysosomal degradation. Surprisingly, it also uses factors previously unrelated to managing protein aggregation but known to be involved in the host’s response to natural pathogens that specifically affect the digestive tract.
The team went on to uncover the way that the SAPA mechanism prevents protein accumulation. By closely tracking the production of an aggregating protein and the aggregation dynamics, the team found that the newly discovered mechanism recognises and eliminates newly synthesised proteins before they can form large aggregates.
Dr David summarised, “A big conundrum in our efforts to understand neurodegenerative disease is why particular areas of the brain show aggregates and others don’t. The existence of local protective mechanisms could help explain why some brain areas are more resistant to protein aggregation. More widely, our fundamental research in this area is important to inform therapeutic interventions for diseases of protein aggregation as well as ways to prevent undesirable protein aggregation that occurs with age.”

Researchers have discovered a new way to target and kill cancer cells in hard-to-treat brain tumours using electrically charged molecules to trigger self-destruction, that could be developed into a spray treatment used during surgery.
A multidisciplinary team of researchers from the University of Nottingham, led by the School of Pharmacy found a new way to harness the extraordinary capabilities of bio-nanoantennae — gold nanoparticles intricately coated with specialised redox active molecules to induce programmed cell death, or apoptosis, in cancer cells on electrical stimulation. The research has been published today in Nature Nanotechnology.
The research focuses on patient-derived Glioblastoma cells, an elusive and formidable form of brain cancer that has long evaded effective treatment. The five-year survival rate for glioblastoma is only 6.8% and the average length if survival for patients is estimated to be only 8 months from diagnosis.
The bio-nanoantennae were able to specifically target glioblastoma cells, leaving healthy cells unscathed. This unprecedented level of precision opens up new possibilities for developing treatment for Glioblastoma during surgical resection of the tumour, when the bio-nanoantennae would be sprayed or injected.
The researchers, which included experts from the Schools of Engineering, Physics and Medicine have now established what is thought to be the first ‘quantum therapeutic’, which taps into the potential of quantum signalling to combat cancer.
Dr Frankie Rawson led the research and explains: “The team showed that cancer cells succumb to the intricate dance of electrons, orchestrated by the enchanting world of quantum biology. With the advent of bio-nanoantennae, this vision of real-world quantum therapies edge closer to reality. By precisely modulating quantum biological electron tunnelling, these ingenious nanoparticles create a symphony of electrical signals that trigger the cancer cells’ natural self-destruction mechanism.”
The team has now secured MRC impact acceleratory funding, have filed patent, to begin translating the technology to this eventual clinical application. Further rigorous research and validation are essential to ensure the safety and effectiveness of bio-nanoantennae for human use.
Dr Ruman Rahman from the School of Medicine and co-author of the study, adds: “Treating Glioblastoma tumours has long presented challenges for clinicians and prognosis for patients is still poor, which is why any research showing the promise of a new effective treatment is hugely exciting. This research has shown the possibilities presented by quantum therapeutics as a new technology to communicate with biology. The fusion of quantum bioelectronics and medicine brings us one step closer to a new treatment paradigm for disease. “

Although a simple molecule, nitric oxide is an important signal substance that helps to reduce blood pressure by relaxing the blood vessels. But how it goes about doing this has long been unclear. Researchers at Karolinska Institutet in Sweden now present an entirely novel principle that challenges the Nobel Prize-winning hypothesis that the substance signals in its gaseous form. Their findings are presented in the journal Nature Chemical Biology.
That the simple molecule nitric oxide or nitrogen monoxide (NO) serves as a signal substance in many important physiological processes has been known for some time. For example, the discovery of the compound’s significance was awarded the 1998 Nobel Prize in Physiology or Medicine. One of its functions is to initiate a signalling cascade that causes the smooth muscles of the vasculature to relax, thus expanding the vessels and lowering blood pressure. This is also why nitroglycerin, which releases NO, has long been a common treatment for angina.
However, the results now presented surprisingly indicate that it is not the NO molecule per se that is the active partner in the chemical interaction.
Can mean a paradigm shift
“It’s a little controversial, something of a paradigm shift in the field, in fact,” says Professor Jon Lundberg, who is the main author of the paper together with Andrei Kleschyov and Mattias Carlström, all of whom are at the Department of Physiology and Pharmacology, Karolinska Institutet.
The NO is formed in the endothelium, the tissue that constitutes the inner lining of blood vessels. For almost 40 years, the hypothesis has been that it then diffuses as a gas, spreading out randomly until it encounters an enzyme called guanylyl cyclase in the vascular smooth muscle, upon which the vessel relaxes. It is a journey over a distance of less than a millimetre, but it is a long way for a molecule.
“It’s hard to believe that it can work, since NO is so reactive and volatile that it ought to have trouble surviving that journey,” says Professor Lundberg.

The study across three countries led by the Department of Psychology’s Dr Paul Hanel discovered people who prioritised achievement over enjoyment were less happy on the next day.
Whereas those who aimed for freedom said they had a 13% increase in well-being, recording better sleep quality and life satisfaction.
And participants who tried to relax and follow their hobbies recorded an average well-being boost of 8% and a 10% drop in stress and anxiety.
Dr Hanel worked with colleagues at the University of Bath on the Journal of Personality-published study.
For the first time, it explored how following various values impacts our happiness.
Dr Hanel said: “We all know the old saying ‘All work and no play makes Jack a dull boy’ and this study shows it might actually be true.
“There is no benefit to well-being in prioritising achievement over fun and autonomy.

It’s a skin disorder that makes life miserable for around 800 million teenagers and adults worldwide, but Australian scientists may have found an effective treatment for acne, delivered via tiny nanoparticles.
In a study led by the University of South Australia (UniSA), a new antibacterial compound known as Narasin was encased in tiny, soft nanoparticles 1000 times smaller than a single strand of human hair and applied in a gel form to targeted acne sites.
The drug — more commonly used in the livestock industry — proved successful against drug-resistant acne bacteria and delivered via nanocarriers achieved a 100-fold increase in absorption than simply taken with water.
The findings have been published in the journal Nanoscale.
Lead author UniSA PhD student Fatima Abid says this is the first time that nano-micelle formulations of Narasin have been developed and trialled.
“Acne severely impacts approximately 9.4% of the world’s population, mainly adolescents, and causes distress, embarrassment, anxiety, low self-confidence and social isolation among sufferers,” Abid says.
“Although there are many oral medications prescribed for acne, they have a range of detrimental side effects, and many are poorly water soluble, which is why most patients and clinicians prefer topical treatments.”
Abid’s supervisor, pharmaceutical scientist Professor Sanjay Garg, says a combination of increasing antibiotic resistance and the ineffectiveness of many topical drugs to penetrate hair follicles in acne sites means there is a pressing need to develop new antibacterial therapies that are effective and safe.

Published36 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Hugh SchofieldBBC News, ParisFrance is set to ban disposable e-cigarettes – known locally as “puffs” – because of the danger they pose to the environment and public health.Speaking recently on RTL radio, Prime Minister Élisabeth Borne said the measure was part of a new anti-smoking plan being drawn up by the government. It should be in force by the end of the year, campaigners said.Several other countries in Europe, including Germany, Belgium and Ireland, have announced similar bans. The UK is also said to be considering one.Sold over the counter by tobacconists, disposable vapes in France cost around €9 (£7.70) – less than a packet of 20 cigarettes. They are supposed to offer around 600 puffs – the rough equivalent of 40 cigarettes.But France’s National Academy of Medicine described them as a “particularly sly trap for children and adolescents”. According to Élisabeth Borne, “they create a reflex, a gesture, which children get used to, and then end up being drawn to tobacco”.Campaigners accuse manufacturers – many based in China – of deliberately targeting teenagers, using bright colours and a range of flavours reminiscent of the sweet shop, for example marshmallow, chocolate and hazelnut, watermelon, and ice candy.Flo PernetIt’s become an epidemic. It is terrible how the tobacco industry has set out to hook children Loïc JosseranPresident of Alliance Against TobaccoAccording to the Alliance Against Tobacco (ACT), 13% of 13-16-year-olds have tried “puffs” at least once. Most say they started around the ages of 11 or 12.”[The ban] is a great victory for civil society. These disposable e-cigarettes are acting as a gateway to smoking for young people,” says ACT president Loïc Josseran.”It’s become an epidemic. It is terrible how the tobacco industry has set out to hook children.”Sam, a 16-year-old Paris schoolboy, said he began smoking disposable e-cigarettes two years ago, shortly after they first appeared in France.”They were talking about it a lot on TikTok. It was like a trend. And I thought, yeah why not?”They’re colourful, and in my head they are not as dangerous as tobacco. My favourites are iced grape and apricot. I guess if the ban goes ahead, I will start buying regular vapes.”In theory it is not possible to buy “puffs” if you are under the age of 18, but Sam said it was easy to evade the restriction. According to ACT, tobacconists systematically refrain from asking for proof of age.Campaigners have also highlighted the ecological damage caused by disposable e-cigarettes. In the UK, a study last year by the environmental organisation Material Focus found that more than one million devices were being thrown out every week.”It’s an environmental plague,” a group of French doctors and environmentalists wrote in Le Monde newspaper earlier this year. They said each disposable e-cigarette was made of plastic and contained a non-removable battery with around 0.15 grams of lithium, as well as nicotine salts and traces of heavy metals.More on this storyHow dangerous is vaping?Published1 day agoTeen vaping: ‘I’ll have puffs as I’m falling asleep’Published4 SeptemberYouth vaping crisis clouds New Zealand’s smoke-free futurePublished13 August

In a trio of papers appearing in Nature on Sept. 13, 2023, the researchers offer the most comprehensive look yet at how malnutrition affects growth in the first two years of life, underscoring a devastating reality for millions of children in the Global South, particularly Asia.
In 2022, more than one in five children around the world — nearly 150 million — did not get enough calories to grow normally, and more than 45 million showed signs of wasting, or weighing too little for their height. More than a million children die each year as a consequence of wasting and more than 250,000 die from stunting. People who experienced stunting and wasting in childhood may also experience worse cognitive development, which translates into worse economic outcomes as adults.
Stunting, or being too short for their age, indicates chronic malnutrition, while wasting measures acute malnutrition. The global health community uses both indications to monitor progress toward ending malnutrition.
“Children whose growth begins to falter before they are six months old are much more likely to die and much more likely to have severe forms of growth faltering by the time they’re 18 to 24 months old,” said the papers’ senior author, Benjamin Arnold, PhD, MPH, associate professor at UCSF’s Francis I. Proctor Foundation. “This suggests there is a very narrow period in which we can intervene, ideally in the prenatal period. It also suggests broader interventions are needed to improve nutrition among women of childbearing age.”
Arnold, an infectious disease epidemiologist and biostatistician, helped lead the research while at UC Berkeley, in conjunction with the (CTML).
Season of birth makes a difference
The analysis involved an international team of more than 100 researchers led by UC Berkeley that examined data on nearly 84,000 children under two years old from 33 major studies that began between 1987 and 2014. The cohorts came from 15 countries in South Asia, Sub-Saharan Africa, Latin America and Eastern Europe.

Researchers at Utah State University have successfully demonstrated that hagfish slime proteins can accurately replicate membranes in the human eye.
Professor Elizabeth Vargis and her team study a condition called age-related macular degeneration that causes damage to the retina, making it difficult to see. They study in vitro models, or a model developed in a laboratory setting, of Bruch’s membrane, a layer in the retina of the eye, to compare the natural aging process to the effects of AMD. They published their research in ACS Biomaterials Science & Engineering this past July.
“By using these models, scientists can better understand the role of Bruch’s membrane in the development of age-related eye diseases,” Vargis said. “This research provides an affordable and widely available option.”
Studying the connection between an aging Bruch’s membrane and deterioration caused by AMD is challenging in live subjects due to the slow progression of the disease and the complexity of isolating specific layers of the retina. Creating an in vitro model of Bruch’s membrane that mimics both its healthy and aged states help researchers understand the relationship between physical changes via aging and AMD. The ideal model should be smooth, nonporous and capable of supporting cell growth. It should also replicate the changes that occur with age in thickness, stiffness and permeability.
Previous models of Bruch’s membrane have captured some of its properties but not all. The most common model is a plastic membrane called a Transwell, which supports cell culture in the retina but is much thicker and stiffer than the natural membrane and cannot easily replicate changes from aging. Other models partially represent Bruch’s membrane but are difficult to produce and/or lack certain crucial aspects required to study AMD.
In previous work with USU Biology Professor Justin Jones, researchers manipulated spider silk proteins to replicate Bruch’s membrane, but challenges in isolating proteins and limited adjustability led to the exploration of other materials. Collaboration with Jones determined that hagfish slime proteins are the best choice for replicating Bruch’s membrane while still maintaining desirable properties. Vargis and her team were able to properly grow retinal cells on hagfish slime proteins and prove that the protein’s behavior changes as the membrane mimic stages of aging and disease.
This study was supported by grants from the NIH, BrightFocus Foundation, and the Office of Naval Research.

Two graduate students from Western University have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury.
Matthew Kolisnyk and Karnig Kazazian combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care.
Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. When patients are admitted to the ICU, families are faced with tremendous uncertainty. Will my loved one recover? Are they aware of what is going on? Will they ever be the same again? Despite these essential questions, health-care professionals are equally uncertain about the potential of a good recovery.
The graduate students are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.
“For years we’ve lacked the tools and techniques to know who is going to survive a serious brain injury,” said Owen.
An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King’s University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.
The team measured brain activity in 25 patients at one of London’s two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.

During a bout of influenza, B cells interact with other immune cells and then take different paths to defend the body. One path is the B cells that differentiate into antibody producing cells. Another path is the B cells that differentiate into lung-resident memory B cells, or lung-BRMs, that are critical for pulmonary immunity.
Unlike antibody-producing B cells that help fight the current infection, the long-lived, non-circulating lung-BRMs migrate to the lungs from draining lymph nodes. They reside there permanently and lie in wait as the first layer of defense that can quickly react to produce antibodies in a future infection.
Understanding the mechanism that creates these lung-BRMs is important for better flu vaccine development. Seasonal influenza kills 290,000 to 650,000 people each year, according to the World Health Organization. Yet flu vaccines are less effective in the elderly — the most at-risk population — compared to younger people. Also, there is need for vaccines that are more effective against later variants of a particular virus.
André Ballesteros-Tato, Ph.D., and colleagues at the University of Alabama at Birmingham have now published a mouse-model study in the journal Immunity showing that interferon-gamma produced by T follicular helper cells, or Tfh cells, after intranasal influenza infection is required to initiate the path of B cell differentiation into lung-BRMs. Ballesteros-Tato is an associate professor in the UAB Department of Medicine Division of Clinical Immunology and Rheumatology.
During influenza infection, both Tfh and B cells are present at germinal centers in the lymph nodes that drain the lungs. Class-switched memory B cells that are primed against the influenza virus begin to appear in the lungs at day 10 of the infection, and their numbers peak at Day 30. However, the UAB researchers found that, if mice were deficient in Tfh cells, or if the Tfh cells were blocked by an antibody, the lung-BRMs did not accumulate. Thus, Tfh cell help is required for class-switched-specific BRM responses to influenza.
What role do the Tfh cells play?
The UAB researchers found that the preferential differentiation of lung-BRMs early after infection correlated with differences in the Tfh cell response early in the viral infection. They found that the number of Tfh cells increased quickly and peaked between days 10 and 15. By Day 10, early in the flu infection, nearly 40 percent of the Tfh cells were producing interferon-gamma, or INF-γ; but that frequency dropped sharply thereafter.