Publisher Health

A research team led by Prof. Yossi Paltiel at the Hebrew University of Jerusalem with groups from HUJI, Weizmann and IST Austria new study reveals the influence of nuclear spin on biological processes. This discovery challenges long-held assumptions and opens up exciting possibilities for advancements in biotechnology and quantum biology.
Scientists have long believed that nuclear spin had no impact on biological processes. However, recent research has shown that certain isotopes behave differently due to their nuclear spin. The team focused on stable oxygen isotopes (16O, 17O, 18O) and found that nuclear spin significantly affects oxygen dynamics in chiral environments, particularly in its transport.
The findings, published in the Proceedings of the National Academy of Sciences (PNAS), have potential implications for controlled isotope separation and could revolutionize nuclear magnetic resonance (NMR) technology.
Prof. Yossi Paltiel, the lead researcher, expressed excitement about the significance of these findings. He stated, “Our research demonstrates that nuclear spin plays a crucial role in biological processes, suggesting that its manipulation could lead to groundbreaking applications in biotechnology and quantum biology. This could potentially revolutionize isotopic fractionation processes and unlock new possibilities in fields such as NMR.”
The story in detail
Researchers have been studying the “strange” behavior of tiny particles in living things, funding some places where quantum effects change biological processes. For example studying bird navigation quantum effects may help some birds find their way in long journeys. In plants efficiently using sunlight for energy is affected by quantum effects.
This connection between the tiny world of particles and living beings likely goes back billions of years when life began and molecules with a special shape called chirality appeared. Chirality is important because only molecules with the right shape can do the jobs they need to in living things.

The World Health Organization has labeled antimicrobial resistance a global threat because most clinical antibiotics are no longer effective against certain pathogenic bacteria. The Center for Antibiotic Discovery and Resistance at the University of Oklahoma, led by Helen Zgurskaya, Ph.D., and Valentin Rybenkov, Ph.D., is working on finding alternative therapeutic solutions.
Antibiotics work by targeting specific parts of a bacteria cell, such as the cell wall or its DNA. Bacteria can become resistant to antibiotics in a number of ways, including by developing efflux pumps — proteins that are located on the surface of the bacteria cell. When an antibiotic enters the cell, the efflux pump pumps it out of the cell before it can reach its target so that the antibiotic is never able to kill the bacteria.
However, OU researchers have contributed to a recent discovery published in the journal Nature Communications. The scientists found a new class of molecules that inhibit the efflux pump and make the antibiotic effective again.
The inhibitors have a novel mechanism of action, which until recently remained unclear. Zgurskaya’s team, in collaboration with teams at the Georgia Institute of Technology and King’s College London in the United Kingdom, have uncovered that these inhibitors work as a “molecular wedge” that targets the area between the inner and outer cell membranes and increases antibacterial activities of antibiotics. Understanding this mechanism can facilitate the discovery of new therapeutics for clinical applications.
“We already live in a post-antibiotic era, and things will get much worse unless new solutions are found for antibiotic resistance in clinics. The discoveries we’ve made will facilitate the development of new treatments to help mitigate an impending crisis,” Zgurskaya said.
Helen Zgurskaya is a George Lynn Cross Research Professor and Valentin Rybenkov is a professor of biochemistry, both in the Department of Chemistry and Biochemistry, Dodge Family College of Arts and Sciences at the University of Oklahoma. Learn more about their research at the Center for Antibiotic Discovery and Resistance.

Results of a long-term, federally funded study of cognitively healthy adults — most with a family history of Alzheimer’s disease — have added to evidence that low spinal fluid levels of a protein linked to learning and memory in mice may serve as an early predictor of mild cognitive impairment (MCI) years before symptoms appear.
The findings, which may potentially offer new targets for treating or preventing Alzheimer’s and other dementias, showed that a relatively low level of the protein known as NPTX2 is not only a likely standalone risk factor for MCI and Alzheimer’s dementia, but also improves prediction of cognitive impairment after accounting for levels of traditional biomarkers and well-established genetic risk factors for Alzheimer’s.
The study, conducted by Johns Hopkins Medicine scientists on more than 250 primarily middle-aged adults, the vast majority of whom were white, concluded that the findings were consistent with and expand prior studies by establishing that measurements of NPTX2 in cerebrospinal fluid were predictive of MCI onset within or even beyond seven years before symptoms occurred.
A report on the study was published July 25 in the Annals of Neurology.
According to the Alzheimer’s Association, MCI, marked by mild memory loss or challenges with other cognitive processes, such as language or executive function, affects up to 18% of people age 60 and older. People with MCI maintain most normal daily activities, but are known to be at higher risk of Alzheimer’s disease or other forms of dementia. It is estimated that 6.7 million Americans age 65 and older are living with Alzheimer’s dementia, with that number expected to double by 2050. The growing prevalence of dementias has given urgency to the search for better and earlier predictors, and targets for treatments that prevent or slow progression. At present, there is only one FDA-approved drug on the market known to even modestly slow symptoms of Alzheimer’s in its early stages, and there are no cures or preventives.
“Our research shows declining levels of NPTX2 occur many years prior to the emergence of MCI or Alzheimer’s symptoms, which raises the possibility of developing new therapeutics that target NPTX2,” says Anja Soldan, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine and corresponding author of the study. “Additionally, it appears that this protein is not a specific marker to just Alzheimer’s, and these findings may be relevant to a variety of other neurodegenerative diseases. So if we can find ways of increasing levels of NPTX2, then it could be applied to identify early and possibly treat other types of memory loss or cognitive impairment as well.”
For the study, which involved adults recruited by the National Institutes of Health and Johns Hopkins Medicine, researchers conducted baseline medical and cognitive exams on 269 cognitively normal individuals, and collected spinal fluid samples biannually. The average age of participants at baseline was 57.7 years. Nearly all were white, 59% were female, most were college educated and 75% had a close relative with Alzheimer’s. NPTX2 levels were measured, as well as the main abnormal proteins found in patients with Alzheimer’s, namely beta-amyloid, total tau and phosphor-tau. Subjects underwent clinical and cognitive assessments for an average of 16 years.

Future therapies to help people live healthy lives for longer could be developed from drugs that release tiny amounts of the gas hydrogen sulfide (H2S), new research has indicated.
A study from the University of Exeter, funded by the US Army and charity The United Mitochondrial Disease Foundation, found that targeting tiny amounts of H2S to specific areas of cells in adult worms using a H2S-releasing molecule called AP39, greatly improved health and activity as they aged. The research, published in PNAS, concludes that targeting H2S specifically to the energy-generating machinery of cells (mitochondria) could one day be used as a healthy aging therapeutic.
The research team administered AP39 to some worms from birth, and to others after reaching adulthood. They found that this compound improved the integrity of mitochondria — the “power house” of cells, which produces our cells’ energy, and kept the worms’ muscles active and moving, even well into old age, and when given mid-way through their life-course.
A number of age-related conditions are linked to loss of mitochondrial function, including natural ageing, neurodegenerative diseases such as Parkinson’s and Alzheimer’s as well as muscular dystrophy and primary mitochondrial diseases.
The team also found a group of proteins that regulated how genes are expressed in ageing (transcription factors). There transcription factors were found to be specifically targeted by H2S. This insight may identify new targets for therapy in ageing and age-related conditions, particularly conditions affecting muscle.
Senior author Professor Tim Etheridge, of the University of Exeter, said: “Worms are a powerful genetic tool to study human health and disease and offer a strong platform to quickly identify new potential therapeutics. Diseases related to ageing take a huge toll on society. Our results indicate that H2S, administered to specific parts of the cell in tiny quantities, could one day be used to help people live healthier for longer
In previous research, the team had found that they could successfully target skeletal muscle with H2S in worms, and the new paper represents the first time this technique has been applied to natural ageing.
The University of Exeter has assigned the underlying technology to its spin-out MitoRx Therapeutics, which has developed next generation compounds with much better drug characteristics as potential medicines to combat diseases of ageing including neurodegenerative disorders such as Huntington’s disease as well as rare childhood conditions such as muscular dystrophy.
Co-author Professor Matt Whiteman, from the University of Exeter, said: “This study is not about extending life — it’s about living healthier lives well into older age. This could have huge benefits to society. We’re excited to see this research move to the next stages over the coming years, and hope it will one day form the basis of new treatments which we have the potential to develop with MitoRx.”
“We saw a small extension of lifespan in the worms that were targeted with H2S, and what’s unique here is that we extended healthspan — or the time they lived healthy lives. The worms still died, albeit later than normally expected, but they died very active and with young physiology.”

Early on, every stem cell faces a fateful choice. During skin development, for instance, the embryonic epidermis begins as a single layer of epidermal progenitor cells. Their choice is to become a mature epidermal cell or switch to becoming a hair follicle cell. This so-called fate switch is governed by the transcription factor SOX9. If the progenitor cell expresses SOX9, hair follicle cells develop. If it doesn’t, epidermal cells do.
But there is a dark side to SOX9, as it’s implicated in many of the deadliest cancers worldwide, including lung, skin, head and neck, and bone cancer. In skin, some aberrant adult epidermal stem cells later turn on SOX9 despite their chosen path — and never turn it off, kickstarting a process that ultimately activates cancer genes.
Scientists have never fully understood how this doomed outcome ensues at a molecular level. But now Rockefeller researchers have revealed the mechanisms behind this malignant turn of events. SOX9, it turns out, belongs to a special class of proteins that govern the transfer of genetic information from DNA to mRNA. That means it has the ability to pry open sealed pockets of genetic material, bind to previously silent genes within, and activate them. They published their results in Nature Cell Biology.
“Our discovery provides new insights into how cancer derails a stem cell’s carefully tuned decision-making process, thereafter making it impossible for it to make normal tissue,” says Elaine Fuchs, head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. “It also illuminates new SOX9-activated genes as potential therapeutic targets.”
Rare keys to gene expression
Our genome is not an open book. In fact, it’s more like a library filled with a few billion books that are mostly under lock-and-key — the majority of genetic material actually lies silent within non-coding and tightly bound packets of DNA cordoned off by histone proteins in a closed state. Together the DNA and histones form what’s called closed chromatin. The genes that are packaged into this cloistered material is inaccessible to the transcription proteins, or factors, that would help it to express the genes within.
But there are a few rare keys that aren’t simply transcription factors. These “pioneer factors” can unlock those genetic packets. They possess the superpower to peer inside the closed chromatin and recognize binding sites within. They then recruit other transcription factors to help them pry open the closed chromatin and bind to receptor sites on the nucleosome, which reprograms the chromatin and activates new genes.

Tuberculosis (TB) disproportionately affects vulnerable populations including those with limited economic resources, HIV patients, those whose diet is deficient in nutrients and others. Resistant TB (MDR TB) does not respond to first line medications and is difficult to treat, requiring long regimens of 15-20 months that are associated with significant side effects and poor outcomes.
Recently, new six-month regimens have been shown to have better results than the long-term treatments, with improved quality of life and health equity. But these novel regimens have not yet been adopted widely in the United States. In a study “Initial experience with BPaL based regimens for multidrug resistant tuberculosis treatment in Massachusetts” to be published in the International Journal of Tuberculosis and Lung Disease, researchers from Boston University Chobanian & Avedisian School of Medicine document that four patients at Boston Medical Center (BMC) Tuberculosis Clinic were cured of MDR TB with a six-month regimen that included bedaquiline, pretomanid and linezolid (BPaL).
“Our study showed that MDR TB can be successfully treated with a six-month regimen that includes only pills. The shorter duration of therapy and the lesser pill burden will result in a better quality of life, improving health equity and access to therapy for MDR TB patients,” said corresponding author Carlos Acuna-Villaorduna, MD, an adjunct assistant professor of infectious diseases. “BMC is the first site in Massachusetts to use this novel treatment for patients with resistant TB.”
“The novel BPaL regimen is a major advance as it achieves superior outcomes with less side effects in a significantly shorter period of time,” said Acuna-Villaorduna, who cited the collaboration between TB clinicians, public health nurses, pharmacists, microbiologists and public health leaders that allowed BMC to safely implement this cutting-edge treatment.

A new review paper co-authored by two Johns Hopkins pain experts suggests that scrambler therapy, a noninvasive pain treatment, can yield significant relief for approximately 80%-90% of patients with chronic pain, and it may be more effective than another noninvasive therapy: transcutaneous electrical nerve stimulation (TENS). The write-up was published online July 13 in The New England Journal of Medicine.
Scrambler therapy, approved by the U.S. Food and Drug Administration in 2009, administers electrical stimulation through the skin via electrodes placed in areas of the body above and below where chronic pain is felt. The goal is to capture the nerve endings and replace signals from the area experiencing pain with signals coming from adjacent areas experiencing no pain, thereby “scrambling” the pain signals sent to the brain, explains the study’s primary author, Thomas Smith, M.D., the Harry J. Duffey Family Professor of Palliative Medicine at the Johns Hopkins Kimmel Cancer Center and a professor of oncology and medicine at the Johns Hopkins University School of Medicine.
All chronic pain and almost all nerve and neuropathic pain result from two things: pain impulses coming from damaged nerves that send a constant barrage up to pain centers in the brain, and the failure of inhibitory cells to block those impulses and prevent them from becoming chronic, says Smith, who also is the director of palliative medicine for Johns Hopkins Medicine.
“If you can block the ascending pain impulses and enhance the inhibitory system, you can potentially reset the brain so it doesn’t feel chronic pain nearly as badly,” Smith says. “It’s like pressing Control-Alt-Delete about a billion times.”
Many patients “get really substantial relief that can often be permanent,” he says. They receive from three to 12 half-hour sessions.
As a physician who treats chronic pain, Smith says, “Scrambler therapy is the most exciting development I have seen in years — it’s effective, it’s noninvasive, it reduces opioid use substantially and it can be permanent.”
TENS therapy also administers low-intensity electrical signals through the skin, but it uses a pair of electrodes at the sites of pain. Pain relief often disappears when or soon after the electrical impulses are turned off, Smith says. A study cited in the review paper evaluated the impact of TENS in 381 randomized clinical trials, and the authors found a nonstatistically significant difference in pain relief between TENS and a placebo procedure.
Smith and co-author Eric Jyun-Han Wang, M.D., program director of the Johns Hopkins pain medicine fellowship and an assistant professor of anesthesiology and critical care medicine at Johns Hopkins, are available for comment. To schedule an interview, contact Valerie Mehl or Amy Mone.

Researchers at Stanford devised a strange new molecule that could lead to drugs that arm genes and make cancers work against themselves.Within every cancer are molecules that spur deadly, uncontrollable growth. What if scientists could hook those molecules to others that make cells self-destruct? Could the very drivers of a cancer’s survival instead activate the program for its destruction?That idea came as an epiphany to Dr. Gerald Crabtree, a developmental biologist at Stanford, some years ago during a walk through the redwoods near his home in the Santa Cruz mountains.“I ran home,” he said, excited by the idea and planning ways to make it work.Now, in a paper published Wednesday in the journal Nature, Dr. Crabtree, a founder of Shenandoah Therapeutics, which is developing cancer drugs, along with Nathanael S. Gray, a professor of chemical and systems biology at Stanford, and their colleagues report that they have done what he imagined on that walk. While the concept is a long way from a drug that could be given to cancer patients, it could be a target for drug developers in the future.“It’s very cool,” said Jason Gestwicki, professor of pharmaceutical chemistry at the University of California, San Francisco. “It turns something the cancer cell needs to stay alive into something that kills it, like changing your vitamin into a poison.”“This is a potentially new way to turn cancer against itself,” said Dr. Louis Staudt, director of the Center for Cancer Genomics at the National Cancer Institute. Dr. Staudt wrote an editorial to accompany Dr. Crabtree’s paper.Once the treatment is further developed, he added, “I would love to try it in a clinical trial with our patients who have exhausted all other options.”In laboratory experiments with cells from a blood cancer, diffuse large B-cell lymphoma, the researchers designed and built molecules that hooked together two proteins: BCL6, a mutated protein that the cancer relies on to aggressively grow and survive, and a normal cell protein that switches on any genes it gets near.The new construction, a dumbbell shaped molecule, is unlike anything seen in nature. BCL6, at one end of the dumbbell, guides the molecule toward cell-death genes that are part of every cell’s DNA and are used to get rid of cells that are no longer needed. But when a person has diffuse large B cell lymphoma, BCL6 has turned off those cell-death genes, making the cells essentially immortal.A computational model of the molecule TCIP1 that hooked together the BRD4 and BCL6 proteins together.Andrey KrokhotinWhen the dumbbell, guided by BCL6, gets near the cell-death genes, the normal protein on the end of the dumbbell arms those death genes. Unlike other processes in the cell that can be reversed, turning on cell-death genes is irreversible.The new approach could be an improvement over the difficult task of using drugs to block all BCL6 molecules. With the dumbbell-shaped molecules, it is sufficient to rewire just a portion of BCL6 molecules in order to kill cells.The concept could potentially work for half of all cancers, which have known mutations that result in proteins that drive growth, Dr. Crabtree said. And because the treatment relies on the mutated proteins produced by the cancer cells, it could be extremely specific, sparing healthy cells.Dr. Crabtree explained the two areas of discovery that made the work possible. One is the discovery of “driver genes” — several hundred genes that, when mutated, drive the spread of cancer.The second is the discovery of death pathways in cells. Those pathways, Dr. Crabtree said, “are used to eliminate cells that have gone rogue for one reason or other” — 60 billion cells in each individual every day.The quest was to make the pathways driving cancer cell growth communicate with silenced pathways that drive cell death, something they would not normally do.When the hybrid molecule drifted to the cells’ DNA, it not only turned on cell-death genes but also did more. BCL6 guided the hybrid to other genes that the cancer had silenced. The hybrid turned those genes on again, creating internal chaos in the cell.“The cell has never experienced this,” Dr. Staudt said.“BCL6 is the organizing principle of these cancer cells,” he explained. When its function is totally disrupted, “the cell has lost its identity and says, ‘something very wrong is happening here. I’d better die.’”But the main effect of the experimental treatment was to activate the cell-death genes, Dr. Crabtree said. “That is the therapeutic effect,” he said.The group tested its hybrid molecule in mice, where it seemed safe. But, Dr. Staudt noted, “humans are a lot different than mice.”The work is “exciting,” said Stuart L. Schreiber, professor of chemistry and chemical biology at Harvard and a previous collaborator with Dr. Crabtree. But he offered words of caution.What Dr. Crabtree created “is not a drug — it still has a long way to go,” he said.

Scientists have identified a protein that plays a pivotal role in the action of several emerging cancer therapies. The researchers say the discovery will likely aid efforts to fine-tune the use of immunotherapies against several challenging cancers. They report their findings in the journal Cancer Research.
“Most anticancer drugs cause cancer cells to shrivel up and die in a controlled process known as apoptosis. But apoptosis does not usually strongly activate immune cells,” said David Shapiro, a professor of biochemistry at the University of Illinois Urbana-Champaign who led the research with former graduate student Santanu Ghosh. “However, a few emerging cancer therapies cause cancer cells to swell up and burst. The protein we identified, a sodium-ion channel known as TRPM4, is critical for cancer therapies that promote this type of cell death, called necrosis.”
Unlike apoptosis, necrosis strongly signals the immune system to target and cleanup the remains of the dying cells, Shapiro said. “This suggests that treatments that promote necrosis may improve immunotherapies against solid tumors,” he said.
TRPM4 is the first protein mediator of anticancer therapy-induced necrosis to be described, Shapiro said.
In previous work, Shapiro, U. of I. chemistry professor and study co-author Paul Hergenrother and their colleagues developed two drugs — a compound called BHPI and later, a more effective agent known as ErSO — that spur necrosis in solid tumors, dramatically shrinking and often eradicating primary and metastatic tumors in mice. These drugs work by binding to estrogen receptors on cancer cells and pushing a normally protective cellular stress-response pathway into overdrive. This pathway, the “anticipatory unfolded protein response, or a-UPR,” ultimately causes the cell to swell, leak and die.
“Even though we identified the initial steps in the a-UPR pathway that kills cancer cells, the specific proteins that mediate cell swelling, rupture and rapid necrotic cell death remained unknown,” Shapiro said.
To identify the relevant proteins, Shapiro and his colleagues screened breast cancer cells by knocking out each of the roughly 20,000 individual genes in the cancer cells and then treating the altered cells with BHPI or ErSO. Cells that resisted treatments with these agents revealed which genes were essential to the drugs’ effectiveness.

Monash University researchers have uncovered why some intestinal worm infections become chronic in animal models, which could eventually lead to human vaccines and improved treatments.
Parasitic worms, also called helminths, usually infect the host by living in the gut. About a quarter of the world population is afflicted with helminth infections.
They are highly prevalent in developing countries such as sub-Saharan Africa, South America and some tropical countries in Asia. In Australia, they can be a problem in First Nations communities.
Some people can fight off the parasites due to effective immune responses. Some people who fail to develop effective immune responses suffer with a long-lasting chronic infection.
Published in Mucosal Immunology, the Monash Biomedicine Discovery Institute study used animal models to reveal a protective immune feature may be lacking in people who are chronically infected.
They discovered that a group of immune cells called T follicular helper (TFH) cells behaved very differently at cellular and molecular levels during acute, resolving and chronic helminth infection.
This meant that in some models the cells protected against chronic illness but in others they didn’t.