Publisher Health

We need zinc: one-tenth of the proteins in our cells require this metal for their normal functions in all aspects of cell metabolism.
We acquire zinc by eating it — in foods or multivitamin supplements — but up to 30% of people in some parts of the world are at risk for zinc deficiency, which can cause slowed growth, impaired immune function, neurological disorders and cancers. The World Health Organization considers zinc deficiency a leading contributor to disease and death.
Despite zinc’s critical role, however, it has not been clear how the metal gets put into proteins that use it or how our cells respond to zinc deficiency.
Now, a team led by Vanderbilt researchers has described and characterized the first zinc metallochaperone: a protein that puts zinc into other “client” proteins. The findings, reported in the journal Cell, shed light on the public health issue of zinc deficiency and open an entirely new area of biology for exploration.
“There’s been a huge gap in the field of metal biology, where we have been unable to identify metallochaperones. It’s remarkable because so many proteins require metal cofactors,” said Eric Skaar, PhD, MPH, Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology and co-corresponding senior author of the Cell paper.
Andy Weiss, PhD, and Caitlin Murdoch, PhD, postdoctoral fellows in Skaar’s group, are co-first authors of the study describing the zinc metallochaperone, which the researchers — in collaboration with an international gene nomenclature committee — named ZNG1 (for zinc regulated GTPase metalloprotein activator 1).

In efforts to prevent the spread of COVID-19, miniaturizing air curtains for hospital wards, labs, and other health care settings is gaining traction as a viable solution to inadequate face masks or when social distancing is not a realistic option.
In AIP Advances, published by AIP Publishing, researchers in Japan developed a desktop air curtain system (DACS) that blocks all incoming aerosol particles.
“We envisage this system will be effective as an indirect barrier for use in blood-testing labs, hospital wards, and other situations where sufficient physical distance cannot be maintained, such as at a reception counter,” co-author Kotaro Takamure said.
An air curtain, or air door, is a fan-powered ventilation system that creates an air seal over an entryway. Hospitals use them to prevent ambulance fumes and other contaminants from reaching the inside of an emergency room.
One challenge in developing smaller air curtains is fully blocking emitted aerosol particles over time because it is difficult to maintain the air wall over a long distance. As a result, the devices gradually lose air-discharge intensity, creating a turbulent flow that allows infected aerosol particles to escape into the surrounding environment.
The DACS contains a discharge and suction port to help address this problem. A generator at the top of the DACS produces the airflow, which is guided to the suction port at the bottom of the device. This prevents airflow dispersion, thus leading to the collection of all the aerosol particles at the suction port. A high-efficiency particulate air (HEPA) filter can be installed inside the suction port for air purification.
The researchers are developing an accompanying virus inactivation system equipped with ultraviolet light that connects to the suction port. After the air is sanitized with the UV light, it is recirculated to maintain airflow of the air curtain and air pressure in the room.
The researchers tested their device by using an air compressor connected to a mannequin to simulate breathing. Dioctyl sebacate, a widely used solvent that spreads easily, was added to the airflow to create aerosol particles. Particle image velocimetry and high-speed cameras were used to determine the DACS’s blocking effect.
The aerosol particles approaching the DACS abruptly bent toward the suction port, signifying that air curtain flow fully blocked all incoming aerosol particles.
When the researchers placed the mannequin’s arm through the DACS to imitate a blood-collection scenario, they found the airflow above the arm was disrupted. However, the aerosol blocking performance remained unaffected.
The DACS was tested on patients during blood collection at Nagoya University Hospital. The researchers are looking at lowering the suction port, so the arm can be placed below the heart for proper blood collection.
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Antibiotic resistance represents a major public health challenge, associated with a high mortality rate. While bacteriophages — viruses that kill bacteria — could be a solution for fighting antibiotic-resistant pathogens, various obstacles stand in the way of their clinical development. To overcome them, researchers from Inserm, Université Sorbonne Paris Nord and Université Paris-Cité at the IAME Laboratory, in close collaboration with their counterparts at Institut Pasteur and the Paris Public Hospitals Group (AP-HP), have developed a model to better predict the efficacy of phage therapy and possibly develop more robust clinical trials. Their findings have been published in Cell Reports.
The discovery of antibiotics had revolutionized the history of medicine in the 20th century, allowing us to effectively fight bacteria for the first time. However, antibiotic resistance — a phenomenon during which bacteria become resistant following mass, repeated use — has become a major public health issue in recent decades. Each year, these resistant bacteria are estimated to be responsible for 700,000 deaths worldwide. Yet the discovery of new antibacterial agents has been stagnating for several years.
In this context, phage therapy has recently generated renewed interest. This therapeutic approach involves the use of bacteriophages that target and destroy pathogenic bacteria whilst being unable to infect humans. While the concept has been in existence for a long time, its clinical development has been hampered by various limitations. Unlike “conventional” medicines, bacteriophages are complex biologics, whose action in the body, optimal dose, and most effective route of administration are difficult to study and anticipate.
In order to remove some of these obstacles, Jérémie Guedj’s research team at Inserm, in collaboration with Laurent Debarbieux’s team at Institut Pasteur, has developed a new mathematical model to better define the interactions between bacteriophages and pathogenic Escherichia coli bacteria in animals and to identify the key parameters that influence the efficacy of phage therapy.
Supporting clinical development
Various data from in vitro and in vivo experiments were used to construct this model. In particular, the researchers used the bacteriophages’ infection parameters determined in the laboratory (for example, the duration of the infectious cycle of the bacteria, the number of viruses released when a bacterium is destroyed…) and information collected during experiments using a mouse model of lung infection.
Some of the animals were infected with a bioluminescent strain of E. Coli (in order to best monitor it within the body). Among them, some were treated with bacteriophages at different doses and using different routes of administration. The quantities of bacteria and bacteriophages thus measured over time helped to feed the mathematical model and test which were the most important parameters for effective phage therapy.
Using their model, the scientists show that the route of administration is an important parameter to consider when it comes to improving the animals’ survival: the more rapidly it brings the bacteriophages into contact with the bacteria, the more it is effective. In the animal model, the phage therapy administered intravenously was therefore less effective in comparison with the intratracheal route because fewer bacteriophages were reaching the lungs. On the other hand, when administered by intratracheal route, the model suggests that the dose of the medication given has little effect on the efficacy of the therapy.
Another important point is that this model incorporates data on the animals’ immune response in the context of phage therapy. The model confirms and extends the principle that bacteriophages act in synergy with the immune system of infected animals, enabling more effective elimination of pathogenic bacteria.
“In this study, we propose a new approach to streamline the clinical development of phage therapy, which otherwise continues to have its limitations. Our model could be reused to predict the efficacy of any bacteriophage against the bacteria it targets, once a limited number of in vitro and in vivo data are available on its action. Beyond phage therapy, the model could also be used to test anti-infective therapies based on the association between bacteriophages and antibiotics,” concludes Guedj.

Oral health is a public health issue that significantly affects people’s overall health. A recent study of root canal longevity using electronic dental record data from 46,000 root canal patients treated in community dental practices found geographic and procedure disparities, providing real-world insight that can be used to inform dental practice.
Teeth survive about 11 years after a root canal, according to new research from Regenstrief Institute and Indiana University School of Dentistry. The groundbreaking study is the first to analyze records from community dental practices, where most Americans receive dental care.
“The findings of this study give deeper insight into the longevity of dental procedures because it provides real-world data on a wider range of patients, not just those receiving care in large health systems or those who are insured,” said first author Thankam Thyvalikakath, DMD, MDS, PhD, director of the Regenstrief-IU School of Dentistry dental informatics program. “This information can be used to inform dental practice, and help patients and dentists make better care decisions.”
Root canals are an important treatment to maintain natural teeth affected by disease. However, over time, the treated tooth eventually becomes brittle and dies. Understanding the outcomes of the procedure is essential to improving dental treatments.
For this study, the research team gathered deidentified electronic dental records from the National Dental Practice-Based Research Network, consisting of 99 small group and solo dentistry practices from around the country. The data covered more than 46,000 patients who received root canals.
Breaking down the root canal data
Data analysis revealed that the median survival time of a tooth after a root canal is 11.1 years. However, several factors can impact that, including follow-up treatments. Teeth that receive a root canal, and a subsequent filling and crown last about 20 years. Teeth that receive either a filling or a crown after a root canal last around 11 years. Teeth that receive no restorative work after a root canal only last about 6.5 years.

Small cell lung cancer (SCLC) is a malignant disease associated with a particularly high mortality rate. According to a new multicenter study led by MedUni Vienna and conducted in collaboration with researchers from the Czech Republic, Hungary, Slovenia, Sweden and the United States, SCLC can be divided into several subgroups in terms of clinical behaviour. These subtypes respond differently to chemotherapeutics and targeted drugs. This opens up possibilities for personalized treatment for this type of cancer as well.
SCLC is a particularly aggressive cancer that typically occurs in smokers, exhibiting rapid growth and a high propensity for metastasis. Recent studies suggest that SCLC may be differentiated into specific molecular subtypes. However, due to the significant lack of tumour material and the problem of tumour heterogeneity, this information could not be effectively validated in a clinical setting.
This new research project has now examined 386 Central European cases, one of the largest cohorts of surgically treated patients to date. The results confirmed that differential expression of ASCL1, NEUROD1, and POU2F3 proteins in tumour tissue defines biologically distinct SCLC subtypes that also have different disease outcomes in surgically resected individuals.
Personalized approach to treatment and follow-up
“In contrast to the increasingly personalized approaches observed in non-small cell lung cancer, SCLC is still considered to be a homogeneous clinical picture and is treated in a standardized way both in hospitals and laboratories,” explains first author Zsolt Megyesfalvi from the Translational Thoracic Oncology Lab at the Medical University of Vienna’s Department of Thoracic Surgery. “We are now showing that differential expression of key transcriptional regulators clearly distinguishes five major SCLC subtypes.” The results also show that high ASCL1 protein expression is an independent negative prognostic marker, whereas high POU2F3 protein expression is associated with more favourable survival outcomes.
Differential response to therapies
The researchers also comprehensively profiled protein expression using mass spectrometry-based proteomics in SCLC cell lines to assess the therapeutic relevance of each SCLC subtype. Study leader Balazs Döme, Head of the Translational Thoracic Oncology programme at the Medical University of Vienna, commented: “We were able to use experiments with tumour cells to show that the levels of subtype-defining markers also influence the response to various targeted and chemotherapeutic agents in vitro. Notably, high POU2F3 expression, which is associated with better survival, correlated with sensitivity to standard chemotherapeutics. In contrast, high YAP1 protein expression correlated with poor response to chemotherapy. In addition, the abundance of subtype-defining proteins was also associated with the efficacy of certain targeted drugs such as CDK, AURK, and IGF-1R inhibitors.”
The study is of great clinical relevance, since it sheds light on the diversity of SCLC and helps to facilitate the implementation of subtype-specific personalized approaches to treatment and follow-up strategies in this disease.
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Human beings, like most organisms, are constantly exposed to alternating colder or warmer temperatures. These environmental variations cause striking metabolic effects and require constant adaptations. While some of these adaptations confer certain beneficial effects on health, the impact of cold and warmth on the various organs in a whole-body context was not known. To understand the overall biological mechanism at stake, a team from the University of Geneva (UNIGE) analysed changes in gene expression simultaneously in various organs in mice. They discovered that all organs strongly react to temperature changes, each showing its own specific modulation. To stimulate research and potential therapeutic applications, the scientists created a web-based application where thousands of gene expression profiles are freely accessible. These results can be read in the journal eLife.
Temperature is one of the main environmental factors to which living beings are subjected. Exposure to cold or warmth has striking effects on metabolism and health, and the implication of temperature on the human health is also evident by the geographic distribution of the incidence of certain diseases. But beyond the physiological response of some tissues, to which extend living in a colder or warmer environment does contribute to whole-body biological changes?
“In our previous studies, we had already observed that temperature had major effects on the functioning of certain organs,” explains Mirko Trajkovski, Professor in the Department of Cell Physiology and Metabolism and in the Diabetes Centre in the UNIGE Faculty of Medicine, who directed this research.
“We now know that exposure to cold promotes weight loss due to the increased thermogenesis, and alleviates the symptoms of multiple sclerosis, while exposure to warmth has protective effects on certain age-related diseases, such as osteoporosis. But what happens on the scale of the whole organism? Indeed, our previous results point to context-dependent effects of temperature alterations on various organs and diseases, but the overall adaptation of the organism needs to be addressed in an integrative way.”
All organs react differently
To address this aim, the scientists analysed the expression of genes in eleven organs (all adipose (fat) tissues, muscle, liver, brain, hypothalamus, ileum, spinal cord, spleen and bone marrow) of three groups of mice exposed to a temperature of 10°C, 22°C, or 34°C. “The data show that the whole body profoundly reacts to temperature changes,” says Mirko Trajkovski. “However, there is no uniformed response: each organ changes its gene expression in its own way, somewhat differently from the rest of the tissues.”
To better understand whether this phenomenon was due to the unique expression of genes specific to each organ, the research team performed additional analyses, focusing on genes that are expressed in all organs. And even when considering only this restricted set of genes, the differences in activation were still striking.
Towards therapeutic recommendations?
“Knowing that exposure to alternating temperatures causes major effects on metabolic diseases such as obesity and osteoporosis, or even on auto-immune diseases, indicates use of temperature shifts as potential therapeutic lifestyle intervention. However, we first need to decipher the temperature-induced effects in an integrative manner throughout the body, and not only at a single organ level. Our work allows precisely that — investigating and understanding the mechanisms at work in various organs simultaneously” says Mirko Trajkovski.
To accelerate research in this emerging field, the Geneva team created a free-to-use and easily accessible web-based application that allows users, both scientists as well as the general public, to search for the expression of thousands of genes in response to exposure to cold or warmth in various organs. “These results will be most useful if they are shared and exploited by a large number of people,” concludes Mirko Trajkovski.
Link to the application and the database: https://metlabomics.unige.ch/Search
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In a study published in the journal Nature Communications, Andrea Mundl-Petermeier and Sebastian Viehmann of the Department of Lithospheric Research at the University of Vienna have demonstrated that a new geochemical archive — 182Tungsten in banded iron formations — can be used to simultaneously trace both the evolution of the Earth’s mantle and continents throughout Earth’s history. This offers new opportunities to better understand the Precambrian Earth in the future.
In order to investigate how the Earth’s mantle developed in the early Earth period, the short-lived 182Hafnium-182Tungsten isotope system has been in the focus before: 182Tungsten indicates, among other things, how much the Earth was exposed to intense meteorite impacts towards the end of its formation and how quickly Earth’s mantle mixed and homogenized with these meteoritic components throughout Earth’s history.
However, until now, magmatic rocks from different, but very limited relicts of ancient continents — for example, Australia or South Africa — had to be studied for these isotopes. Andrea Mundl-Petermeier and Sebastian Viehmann from the Department of Lithospheric Research at the University of Vienna and colleagues at the University of Cologne and Jacobs University Bremen, now discovered a new geochemical archive published it in the journal Nature Communications: tungsten isotope signatures in banded iron formations (BIFs), which predominantly formed in the Precambrian, i.e., between 3.8 billion and about 540 million years ago.
Evolution of the Earth’s mantle and the continents
Using the 2.7 billion-year-old iron formation from the Temagami greenstone belt in Canada, the team was able to reconstruct that iron- and silica-rich layers deposited from seawater can simultaneously record the evolution of the Earth’s mantle and crust. With state-of-the-art instruments from the GeoCosmoChronology group and the new Geoscience Solid State Mass Spectrometry (GeoIsotopes) Core Facility at the Department of Lithospheric Research, the research team obtained high-precision isotope measurements of individual bright quarz and dark iron layers.
“With the help of high-precision measurement methods, we were able to resolve small but distinct differences in 182W of individual layers,” says Andrea Mundl-Petermeier from the Department of Lithospheric Research. The new approach now tackles the long-standing questions regarding mantle and crust evolution from a seawater perspective: banded iron ores are formed by chemical deposition from the ocean. “The BIFs studied from the Temagami area thus directly represent seawater chemistry 2.7 billion years ago,” explains geologist Sebastian Viehmann: “We are looking at the Earth at that time from the perspective of the ocean.”
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A small group of researchers including Dennis Kurzbach from the Faculty of Chemistry of the University of Vienna just published in Nature Protocols an advanced NMR (Nuclear Magnetic Resonance) method to monitor fast and complicated biomolecular events such as protein folding.
For example, protein folding was long considered as one of the great mysteries of modern research. This crucial process during which amino acid chains adopt a 3D structure and functionality, takes place within milliseconds. Being this fast, protein folding events could often not be characterized by NMR spectroscopy; the standard method for studying molecular structures. Employing hyperpolarized water, researchers have now developed a method that dramatically enhances the signals of the proteins, nucleic acids, and other biomolecules. This renders monitoring of processes such as protein folding possible.
Enabling real-time NMR
With NMR spectroscopy, researchers can measure the magnetic properties of atoms and thus analyse the atomic structure of molecules in solution. The method of Dennis Kurzbach and his colleagues Christian Hilty (USA) and Lucio Frydman (Israel) is based on NMR and enables the monitoring of biological processes in real-time. By using hyperpolarised water, the researchers significantly enhanced NMR signals of the investigated samples and therefore boost the method’s sensitivity.
With hyperpolarization methods, more precisely dissolution DNP (D-DNP), a signal enhancement of over 10,000-fold is possible. “The hyperpolarized water acts as a booster for the NMR signals of a protein during the measurement. The hydrogen nuclei of the hyperpolarized water are exchanged with those of the proteins, thus transferring the signal strength to the latter,” says Dennis Kurzbach from the Institute of Biological Chemistry and deputy head of the NMR Centre of the Faculty of Chemistry.
With the new method, the researchers can record an NMR spectrum every 100 milliseconds and use it to track the 3-D coordinates of individual amino acids and how they change over time. “This allows us to monitor processes that occur in milliseconds and distinguish individual atoms,” says chemist Dennis Kurzbach, who focuses in his research on developing new methods.
Increasing use of NMR for protein analyses
In their study the authors describe their technique in detail, from hyperpolarization to the transfer of the hyperpolarized water to the NMR spectrometer, to the mixing of the hyperpolarized water with the sample solution, and the NMR measurement.
In addition, they present six examples for method application, including the observation of protein folding or even the interactions of RNA (nucleic acids) and RNA-binding proteins as the basis for gene expressions in the cell. According to the scientists, the new method can be used for specific studies of RNA, DNA and polypeptides, especially when signal enhancement reaches the ‘magic’ number of 1,000-fold.
An NMR spectrometer equipped with a hyperpolarization prototype is a prerequisite for NMR boosted by hyperpolarized water. However, this kind of infrastructure is not common yet. The Faculty of Chemistry of the University of Vienna is equipped with a DDNP-NMR device since 2020, which has been constructed by Dennis Kurzbach based on an ERC Starting Grant.
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Some treatments or preventive therapies used to manage intracerebral hemorrhages (ICH), or a bleeding stroke, are not as effective as previously believed, according to the new American Heart Association/American Stroke Association guideline for caring for people with spontaneous ICH, published today in the Association’s Stroke journal. Guidelines detail the latest, evidence-based treatment recommendations and are the Association’s official clinical practice recommendations.
The guideline includes recommendations on surgical techniques, individual activity levels after an ICH, and additional education and training for at-home caregivers. It reflects the steady informational gains made in the intracerebral hemorrhage field since the last guideline on ICH management was published in May 2015.
“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures and the underlying disease in small blood vessels,” says Steven M. Greenberg, M.D., Ph.D., FAHA, chair of the guideline writing group, a professor of neurology at Harvard Medical School and vice chair of neurology at Massachusetts General Hospital, both in Boston.
ICH accounts for about 10% of the nearly 800,000 strokes that occur annually in the U.S. Typical causes of primary ICH (i.e., ICH not due to another condition such as head trauma) include uncontrolled high blood pressure and age-related degeneration of the brain’s blood vessels. ICH is also one of the deadliest types of strokes, with a 30% to 40% death rate. ICH affects Black and Hispanic people at a rate 1.6 times higher than white people according to U.S. studies. Worldwide, stroke (of any kind) is the second-leading cause of death and a leading cause of long-term disability.
The likelihood of an ICH increases sharply with age, so as the population gets older, these types of strokes are expected to remain a significant health concern. Additionally, the widespread use of blood thinners is a growing cause of ICH. Therefore, new treatments for ICH and improved use of evidence-based approaches are needed for ICH prevention, care and recovery.
Updates to Standard Care Practices
The new guideline suggests that many techniques widely considered “standard care” are not necessary. For example, research confirms that wearing compression socks or stockings of any length to prevent deep vein blood clots, known as deep vein thrombosis, after a bleeding stroke is not effective. Instead, a method known as an intermittent pneumatic compression, which involves wrapping the lower legs and feet in inflatable boots, may be helpful if started on the same day of an ICH diagnosis. Further information is needed, though, on whether using compression stockings in combination with medication may prevent blood clots from developing.

A USC Stem Cell study in NPJ Regenerative Medicine presents intriguing evidence that large bone injuries might trigger a repair strategy in adults that recapitulates elements of skeletal formation in utero. Key to this repair strategy is a gene with a fittingly heroic name: Sonic hedgehog.
In the study, first author Maxwell Serowoky, a PhD student in the USC Stem Cell laboratory of Francesca Mariani, and his colleagues took a close look at how mice are able to regrow large sections of missing rib — an ability they share with humans, and one of the most impressive examples of bone regeneration in mammals.
To their surprise, the scientists observed an increase in the activity of Sonic hedgehog (Shh), which plays an important role in skeletal formation in embryos, but hasn’t previously been linked to injury repair in adults.
In their experiments, Shh appeared to play a necessary role in healing the central region of large sections of missing ribs, but not in closing small-scale fractures.
“Our evidence suggests that large-scale bone regeneration requires the redeployment of an embryonic developmental program involving Shh, whereas small injuries heal through a distinct repair program that does not mirror development,” said Mariani, the study’s corresponding author and an associate professor of stem cell biology and regenerative medicine at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC.
Serowoky added: “It’s still a fascinating mystery which factors or conditions result in Shh activity following large, but not small bone injuries.”
In mice, Shh activity increased briefly after a large rib injury, and then quickly returned to normal levels within 5 days. Although transient, this increase in Shh was a prerequisite for successfully building a callus, which is an initial scaffold that bridges a fracture or injury but then converts to bone and regenerates the missing section of rib. Mice genetically modified to lack Shh couldn’t successfully form calluses or heal their ribs.
In contrast, mice that had Shh at the time of injury, but were genetically altered to lose Shh after a 5-day healing period, were able to repair their ribs normally. A related gene known as Smoothened (Smo) was also required only during the first 5 days of the healing process.
The researchers expected that the source of Shh would be from specific progenitor cells that the group had previously shown to be essential for healing large injuries and that reside in the periosteum, which is the sheath of tissue surrounding each rib. Instead, they discovered that the source of Shh was an unexpected population of stem cell-like cells, known as mesenchymal cells. When these mesenchymal cells increased their Shh activity, this seemed to serve as a signal to summon a separate population of stem cell-like bone marrow cells to the injury site to assist in the healing process.
“Our discovery may inform future therapeutic strategies for situations where patients are missing large sections of bone following high energy injuries such as traffic accidents or combat wounds, or after cancer-related bone resections,” said co-author Jay R. Lieberman, chair and professor of orthopaedic surgery at the Keck School.
Additional co-authors for this USC study include Stephanie Kuwahara and Shuwan Liu from the Department of Stem Cell Biology and Regenerative Medicine, and Venus Vakhshori from the Department of Orthopaedic Surgery.
The majority of this work (90%) was supported by federal funding from the National Institutes of Health (T32HD060549, R01AR069700, R01AR057076), and the remainder was supported by a Roy E. Thomas Graduate Fellowship and a USC Regenerative Medicine Initiative Award, which provided the initial pilot funding to bring together the basic researchers and surgeon-scientists who collaborated on this stem cell study.
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Materials provided by Keck School of Medicine of USC. Original written by Cristy Lytal. Note: Content may be edited for style and length.