Publisher Health

In a new breakthrough to understand more about the mammalian brain, University of Copenhagen researchers have made an incredible discovery. Namely, a vital enzyme that enables brain signals is switching on/off at random, even taking hours-long “breaks from work.” These findings may have a major impact on our understanding of the brain and the development of pharmaceuticals. Today, the discovery is on the cover of Nature.
Millions of neurons are constantly messaging each other to shape thoughts and memories and let us move our bodies at will. When two neurons meet to exchange a message, neurotransmitters are transported from one neuron to another with the aid of a unique enzyme.
This process is crucial for neuronal communication and the survival of all complex organisms. Until now, researchers worldwide thought that these enzymes were active at all times to convey essential signals continuously. But this is far from the case.
Using a groundbreaking method, researchers from the University of Copenhagen’s Department of Chemistry have closely studied the enzyme and discovered that its activity is switching on and off at random intervals, which contradicts our previous understanding.
“This is the first time anyone has studied these mammalian brain enzymes one molecule at a time, and we are awed by the result. Contrary to popular belief, and unlike many other proteins, these enzymes could stop working for minutes to hours. Still, the brains of humans and other mammals are miraculously able to function,” says Professor Dimitrios Stamou, who led the study from the center for Geometrically Engineered Cellular Systems at the University of Copenhagen’s Department of Chemistry.
Until now, such studies were carried on with very stable enzymes from bacteria. Using the new method, the researchers investigated mammalian enzymes isolated from rats’ brains for the first time. Today, the study is published and placed on the cover of the scientific journal Nature.

A vaping habit could end up leading to a tarnished smile, and more frequent visits to the dentist.
Research by faculty from Tufts University School of Dental Medicine found patients who said they used vaping devices were more likely to have a higher risk of developing cavities. With CDC surveys reporting that 9.1 million American adults — and 2 million teenagers — use tobacco-based vaping products, that means a lot of vulnerable teeth.
The findings of this study on the association between vaping and risk of caries — the dental term for cavities — serve as an alert that this once seemingly harmless habit may be very detrimental, says Karina Irusa, assistant professor of comprehensive care and lead author on the paper. The study was published November 23 in The Journal of the American Dental Association.
Over the last few years, public awareness has increased about the dangers of vaping to systemic health — particularly after the use of vaping devices was tied to lung disease. Some dental research has shown ties between e-cigarette use and increased markers for gum disease, and, separately, damage to the tooth’s enamel, its outer shell. But relatively little emphasis has been placed on the intersection between e-cigarette use and oral health, even by dentists, says Irusa.
Irusa says that the recent Tufts finding may be just a hint of the damage vaping causes to the mouth. “The extent of the effects on dental health, specifically on dental decay, are still relatively unknown,” she says. “At this point, I’m just trying to raise awareness,” among both dentists and patients.
This study, Irusa says, is the first known specifically to investigate the association of vaping and e-cigarettes with the increased risk for getting cavities. She and her colleagues analyzed data from more than 13,000 patients older than 16 who were treated at Tufts dental clinics from 2019-2022.

Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now, investigators have reported highly promising early results for CAR T therapy in a small set of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June, MD, and Daniel Baker, a doctoral student in Cell and Molecular Biology in the Perelman School of Medicine at the University of Pennsylvania, discuss this development in a commentary published today in Cell.
“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” said June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center.
T cells are among the immune system’s most powerful weapons. They can bind to, and kill, other cells they recognize as valid targets, including virus-infected cells. CAR T cells are T cells that have been redirected, through genetic engineering, to efficiently kill specifically defined cell types.
CAR T therapies are created out of each patient’s own cells — collected from the patient’s blood, and then engineered and multiplied in the lab before being re-infused into the patient as a “living drug.” The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine, and received Food & Drug Administration approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different cancers. The therapies have revolutionized the treatment of certain B cell leukemias, lymphomas, and other blood cancers, putting many patients who otherwise had little hope into long-term remission.
From the start of CAR T research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams at Penn Medicine and biotech spinoffs who are working to develop effective treatments from Penn-developed personalized cellular therapy constructs, are examining these potential new applications. The commentary from June and Baker comes in response to the first significant clinical report of success from these efforts: a paper in Nature Medicine from German researchers on the use of CAR T therapy against the autoimmune disease lupus (systemic lupus erythematosus).
Researchers say lupus is an obvious choice for CAR T therapy because it too is driven by B cells, and thus experimental CAR T therapies against it can employ existing anti-B-cell designs. B cells are the immune system’s antibody-producing cells, and, in lupus, B cells arise that attack the patient’s own organs and tissues.
In the German study, the patients — five young adults — did not benefit from standard lupus treatments. Yet, all went into remission, and were able to stop taking their lupus drugs within three months of a single, relatively small dose of CAR T therapy, which essentially removed their existing B cells. (Cancer patients subsequently require infusions of purified human antibodies from healthy volunteers, to maintain some antibody immunity.) Even more remarkably, all the patients remained in remission during the follow-up period of up to a year, and unlike cancer patients, the lupus patients experienced the return of their B cells, which are naturally replenished from blood stem cells in bone marrow.
Baker and June note in their commentary that, although the German study’s results need to be confirmed with larger studies and longer-term follow-up, they are highly promising — indeed, they suggest that lupus could turn out to be an easier CAR T target than B-cell cancers.
“Disease-driving B cells are much less numerous in lupus,” Baker said. “Thus, effective CAR T treatment of this autoimmune disease may require a much lower dose that greatly reduces the problem of immunological side-effects.”

Published16 hours agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesBy Madeline HalpertBBC News, WashingtonWith the holiday season approaching in the US, doctors are urging people to exercise caution to avoid a surge in common and potentially dangerous winter viruses.The US is facing a rise in cases of respiratory syncytial virus (RSV), with some hospitals opening extra beds to treat patients, while there are concerns about other illnesses such as flu.Winnie Chow, a parent to ten-month old Cooper, took her son to hospital earlier this month after he had been vomiting and coughing for several days. He spent four days there recovering from RSV.”I was in tears,” said Ms Chow, who lives in Hackensack, New Jersey. “For him to be there for more than a day was very scary.”Ms Chow is one of many parents who have had to seek care for an unwell child as winter viruses arrive earlier and with more severity than in recent years – a trend experts say could persist as people gather indoors for Thanksgiving and Christmas.Image source, Winnie Chow”We do worry when people start gathering,” said Richard Malley, a senior physician with the Division of Infectious Disease at Boston Children’s Hospital in Massachusetts. “When you have multiple generations mingling together, you have an increased risk of transmission from someone who is handling the virus pretty well to someone who may not handle it well at all.”What is RSV and what are the symptoms? RSV can manifest like a common cold in adults, but can prove dangerous for some young children.Symptoms include a cough, congestion, runny nose and fever as well as wheezing in young infants, according to Rachel Orscheln, the director of ambulatory paediatric infectious diseases at St Louis Children’s Hospital.For the most vulnerable, RSV can lead to bronchiolitis, a condition that includes a build-up of inflammation in the lungs and difficulty breathing. There is no vaccine for RSV but scientists are working on developing one.It can be difficult to distinguish between RSV, coronavirus and the flu because the respiratory viruses include many of the same symptoms and usually peak in winter.But physicians can use tests to diagnose patients to determine the best course of treatment.Parents should reach out to their child’s healthcare provider if they begin to have concerns, especially if they are experiencing worsening symptoms, difficulty breathing or are struggling to drink fluids, said Sonali Advani, an assistant professor of medicine at Duke University’s Division of Infectious Diseases.Why are RSV and flu cases rising? Experts say protective measures like social distancing, mask wearing and other hygiene practices from the coronavirus pandemic likely shielded some children from exposure to the flu and their first RSV infection, which most children normally experience by age two. This means they may now be more vulnerable to infection.An earlier RSV season followed by more severe flu infections has created a “perfect storm” that is “flooding our paediatric capacity”, said Daniel Rauch, the chief of Paediatric Hospital Medicine at Tufts Medicine in Massachusetts. He told the BBC a reduction in hospital beds for children during the coronavirus pandemic, which was intended to make space for adults who are more vulnerable to severe illness from Covid, had worsened the current problem.Some experts said they were not optimistic the issues would resolve soon, as close contact during Thanksgiving and the rest of the winter holiday season could offer more opportunities for viral transmission. How to stay safeGetting vaccinated against Covid and the flu offers one of the best forms of protection against some of the respiratory illnesses that are circulating, experts told the BBC.US infectious disease chief Dr Anthony Fauci said the flu jab was “well-matched” to the circulating strain, while White House Covid co-ordinator Dr Ashish Jha urged Americans to “make protecting our loved ones an important part of the conversation we have around the Thanksgiving table”.Image source, Getty ImagesTaking a rapid test for Covid on the morning of Thanksgiving and other winter holidays adds another potential layer of protection, Dr Malley said. He added that parents could also make sure any person serving food during large family gatherings is symptom-free and handling the food in a hygienic manner. Handwashing and avoiding touching your face and mouth are also advised.”If you’re sick, maybe skip the family gathering this year,” Dr Rauch said. “Don’t bring it to everybody else.”Parents and children should also wear masks during travel on planes, trains and other public transportation and could do so during gatherings where they are unsure others are vaccinated, Dr Rauch said. In the meantime, Amy Knight, the president of the Children’s Hospital Association which represents more than 220 hospitals across the US, said paediatric hospitals were “getting creative” and finding extra space for patients while working to keep conditions as normal as possible.”No one likes to have a sick child,” she said.”It’s an incredibly stressful time, but many have also been understanding in recognising that the hospital has a big challenge and a big job, and they’re grateful to be there and grateful to have the care.”Additional reporting by Gareth EvansMore on this storyParents stressed over flu season pain med shortage6 days agoAntibody jab approved in UK for common winter virus RSV10 NovemberFlu and winter virus concern but Covid stays level in UK28 October

A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.
Our brains are bigger, and are guts are shorter than our ape peers.
“A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period,” in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.
Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal Cell.
The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.
“They seem especially specific in causing genes to turn on, we think just in certain cell types at certain times of development, or even genes that turn on when the environment changes in some way,” Lowe said.

Hollow spheres made of MYC proteins open new doors in cancer research. Würzburg scientists have discovered them and report about this breakthrough in the journal Nature.
MYC genes and their proteins play a central role in the emergence and development of almost all cancers. They drive the uncontrolled growth and altered metabolism of tumour cells. And they help tumours hide from the immune system.
MYC proteins also show an activity that was previously unknown — and which is now opening new doors for cancer research: They form hollow spheres that protect particularly sensitive parts of the genome. If these MYC spheres are destroyed, cancer cells will die.
This was reported by a research team led by Martin Eilers and Elmar Wolf from the Institute of Biochemistry and Molecular Biology at Julius-Maximilians-Universität Würzburg (JMU, Bavaria, Germany) in the journal “Nature.” The researchers are convinced that their discovery is a game changer for cancer research, an important breakthrough on the way to new therapeutic strategies.
Hollow spheres protect sensitive DNA sites
What the researchers discovered: When cells in the lab are kept under stress conditions similar to those found in fast-growing tumour cells, the MYC proteins in the cell nucleus rearrange themselves in a dramatic way. They join together to form hollow spheres consisting of thousands of MYC proteins.
The hollow spheres surround and protect individual, particularly sensitive sites in the genome — precisely the sites where two types of enzymes can collide: Enzymes that read DNA to synthesize RNA and enzymes that duplicate DNA. Both can be thought of as two trains travelling on only one track, on DNA.
The hollow spheres thus prevent the two enzymes from colliding. The Würzburg team was able to confirm this observation in cancer cells. If the protective function of the protein spheres is switched off experimentally, collisions of the enzymes occur and, as a consequence, multiple breaks occur in the DNA — which ultimately kill the cancer cells.
Search for specifically effective drugs
“These observations revolutionize our understanding of why MYC proteins are so crucial for the growth of tumor cells,” says Martin Eilers. The new findings also raise the question of whether drugs can be developed that specifically prevent the formation of the hollow spheres.
To drive this development forward, Eilers and Wolf have started a company. Together with JMU and partners from the pharmaceutical industry, the search for drugs that interfere with the newly discovered functions of the MYC proteins has begun.
“The fact that investors made it possible for us to set up so quickly is certainly not an everyday occurrence,” say the JMU professors. They also consider this as a sign that they have made a discovery that is very promising.
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Materials provided by University of Würzburg. Original written by Robert Emmerich. Note: Content may be edited for style and length.

Patients who take statins to lower high cholesterol levels often complain of muscle pains, which can lead them to stop taking the highly effective medication and put them at greater risk of heart attack or stroke.
Some clinicians have recommended vitamin D supplements to ease the muscle aches of patients taking a statin, but a new study from scientists at Northwestern University, Harvard University and Stanford University shows the vitamin appears to have no substantial impact.
The study will be published Nov. 23 in JAMA Cardiology.
Although non-randomized studies have reported vitamin D to be an effective treatment for statin-associated muscle symptoms, the new study, which is the first randomized clinical trial to look at the effect of vitamin D on statin-associated muscle symptoms, was large enough to rule out any important benefits.
In the randomized, double-blind trial, 2,083 participants ingested either 2,000 units of vitamin D supplements daily or a placebo. The study found participants in both categories were equally likely to develop muscle symptoms and discontinue statin therapy.
Over 4.8 years of follow-up, statin-related muscle pain was reported by 31% of the participants assigned vitamin D and 31% assigned a placebo.

Scientists have revealed the inner workings of a key protein involved in a wide range of cellular processes — potentially paving the way for better and less toxic cancer drugs.
Using Nobel Prize-winning microscopy techniques, the researchers revealed how the tankyrase protein switches itself on and off by self-assembling into 3D chain-like structures.
Their study, published in the journal Nature, reveals crucial structural insights into the elusive but important tankyrase protein, which plays a particularly important role in helping drive bowel cancer.
Scientists at The Institute of Cancer Research, London, believe their research will open the door to new types of cancer treatment that can control tankyrase more precisely than is currently possible, with fewer side effects.
The fundamental discovery could have implications for treating various cancers, as well as diabetes and inflammatory, cardiac and neurodegenerative diseases.
The study was mainly funded by Cancer Research UK, Wellcome and The Institute of Cancer Research (ICR), which is itself a charity as well as a research institute.

A single drug compound simultaneously attacks hard-to-treat prostate cancer on several fronts, according to a new study in mice and human cells. It triggers immune cells to attack, helps the immune cells penetrate the tumor, and cuts off the tumor’s ability to burn testosterone as fuel, according to new research from Washington University School of Medicine in St. Louis. The drug may offer a promising new strategy for treating patients whose tumors don’t respond to standard therapy.
The study appears online in the journal Nature Communications.
Prostate cancer is notorious for eventually developing resistance to standard treatments that block or reduce testosterone, which fuels growth of these tumors. And like many solid tumors, prostate cancer also has proven stubbornly resistant to newer immunotherapies, which are intended to take the brakes off the immune system’s T cells to get them fighting cancerous invaders. Immunotherapies — most commonly, immune checkpoint inhibitors — can be extremely effective but only in certain cancers, such as melanoma.
“We need to develop better therapies for prostate cancer patients, because most of these tumors develop resistance to hormone-based therapies doctors rely on to treat these cancers,” said senior author Nupam P. Mahajan, PhD, a professor of surgery. “Immunotherapy is the newest and most promising type of therapeutic for cancer right now, but even so, immune checkpoint inhibitors have failed to do much against most solid tumors, including prostate cancer. This study was surprising because we found that this drug activates anti-cancer T cells in a novel way, and it also increases the T cells’ ability to penetrate the tumor. This could lead to a more effective strategy for patients whose cancers are hard to treat.”
The drug, called (R)-9b, is a small molecule that blocks an oncogene, a gene that drives cancer. The researchers initially attributed the drug’s success in mouse studies to its ability to reduce or eliminate androgen receptors in the prostate cancer cells. These receptors bind to testosterone and use the hormone to fuel tumor growth. The drug’s ability to eliminate the androgen receptor differs from standard drugs that reduce the amount of testosterone in the body, and other drugs that block the androgen receptor’s function as a transcription regulator.
But because the new drug was so effective, Mahajan and his colleagues suspected something more was going on. The drug blocks a gene called ACK1. The researchers developed a strain of mice that totally lacked this gene in order to study what happens when it’s missing. At first, the researchers were baffled by these mice. Mice missing an entire gene often have obvious problems. But these mice seemed fine. And when the researchers looked for tumor growth, they found very little. It was difficult to model cancer in these animals.
“In most of these mice, when we introduced cancer cells as we typically do, there was no trace of a tumor,” said Mahajan, also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “In the few that did develop tumors, the tumors were small compared to those of wild-type mice. This was the first clue that something important was happening in mice missing this gene. We found that they were able to mount a robust immune response against the cancer cells.”
When different mice — mice with this gene — were implanted with human prostate tumors and given the drug that blocks this gene, it had the same effect: taking the brakes off the immune system and producing increased levels of certain types of T cells known to attack cancer. The drug also increased signaling molecules that allow the T cells to penetrate the tumor and kill cancer cells more effectively. The tumors in these (R)-9b treated mice were much smaller than those of mice in control groups.
Given the drug’s success in tumor penetration, the researchers investigated whether adding immune checkpoint inhibitors to treatment with the drug would be even more effective, taking the brakes off T cells in more than one way at the same time — but there was no such improvement.
“Surprisingly, we found that the immune checkpoint inhibitor is activating ACK1, the very pathway we are shutting down with this drug compound,” Mahajan said. “It’s possible immune checkpoint inhibitors don’t work well in these tumors because they are turning on ACK1, which suppresses the immune response. Similar to prostate cancer, the ACK1 pathway activation also could be employed by other cancers that do not respond to checkpoint inhibitors. However, these cancers could respond to (R)-9b, so we would like to investigate this drug in other solid tumors as well.”
Mahajan said the drug spurs multiple responses because of the nature of the gene it blocks. Many genes have several roles in the body, and ACK1’s roles in expression of the androgen receptor and in reigning in the immune system make it an appealing target for cancer therapy, especially against solid tumors with a hormonal growth component, such as prostate and breast cancers.
Mahajan has worked with Washington University’s Office of Technology Management/Tech Transfer to file patents on the use of this drug in cancer treatment. His team is gathering data to apply for permission from the Food and Drug Administration to test the drug in a clinical trial for patients with prostate cancer.

A recent study, affiliated with UNIST has reported a new route for measuring blood sugar levels (BGLs) without drawing blood. This is a revolutionary, non-invasive technique for testing blood glucose levels, using electromagnetic (EM)-wave-based glucose sensor inserted under the skin. Their findings have attracted much attention, as it eliminates the need for patients with diabetes to constantly prick their fingers with a glucose meter.
This breakthrough has been led by Professor Franklin Bien and his research team in the Department of Electrical Engineering at UNIST.
In this study, the research team proposed electromagnetic-based sensor that can be subcutaneously implanted and capable of tracking minute changes in dielectric permittivity owing to changes in BGLs. The proposed sensor, which is about one-fifth of a cotton swab, can measure changes in glucose concentrations in interstitial fluid (ISF), the liquid that fills spaces between cells.
“Present work is an effort for the realization of implantable electromagnetic-based sensor, which can be an alternate to enzyme-based or optical-based glucose sensor,” noted the research team. ‘The proposed implantable sensor has not only overcome the disadvantages of the existing continuous glucose monitoring systems (CGMS), such as short lifespan, but has also enhanced the blood glucose prediction accuracy.”
Diabetes can be diagnosed if fasting blood glucose levels are 126 mg/dL or higher. A normal fasting glucose test result is lower than 100 mg/dL. One of the main aims of diabetes treatment is to keep blood glucose levels within a specified target range. More than 400 million people worldwide are living with diabetes and they still suffer from pricking their fingers multiple times a day to check their blood glucose levels.
Various methods alternate to finger-pricking method have been extensively studied for blood glucose detection, such as enzyme-based or optical-based glucose sensor. Yet, they still have issues in terms of long lifetime, portability, and accuracy.
In this study, the research team introduced semi-permanent and continuous blood sugar management at low maintenance costs without the pain caused by blood collection, enabling patients to enjoy quality life through proper treatment and management of diabetes. This is expected to increase the use of CGMS, which currently stands at only 5%.
The research team also performed both the intravenous glucose tolerance test (IVGTT) and oral glucose tolerance test (OGTT) with sensor implanted to swine and beagle in a controlled environment. The results of initial proof-of-concept in vivo experiment showed promising correlation between BGL and sensor frequency response, according to the research team.
“Our proposed sensor and system are indeed in the early stage of development,” noted the research team. “Despite that, the proof-of-concept in vivo results show promising correlation between BGL and sensor frequency response. Indeed, the sensor shows the ability to track BGL trend.”
“For actual sensor implantation we must consider bio compatible packaging and foreign body reactions (FBR) for long term applications. In addition, improved sensor interface system is under development,” added the research team.
Their findings have been published in the October 2022 issue of Scientific Reports. This study has been carried out in collaboration with SB Solutions Inc., a UNIST-based faculty startup company founded by Professor Franklin Bien (Department of Electrical Engineering, UNIST). The company, founded in 2017, is a developer of a glucose measurement system designed to assists in real-time blood glucose management. The company’s system uses a non-invasive glucose measurement technique based on electromagnetic waves and related systems are currently in the stages of the commercialization process.
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Materials provided by Ulsan National Institute of Science and Technology(UNIST). Original written by JooHyeon Heo. Note: Content may be edited for style and length.