Publisher Health

In a recent study of the brain’s waste drainage system, researchers from Washington University in St. Louis, collaborating with investigators at the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institute of Health (NIH), discovered a direct connection between the brain and its tough protective covering, the dura mater. These links may allow waste fluid to leave the brain while also exposing the brain to immune cells and other signals coming from the dura. This challenges the conventional wisdom which has suggested that the brain is cut off from its surroundings by a series of protective barriers, keeping it safe from dangerous chemicals and toxins lurking in the environment.
“Waste fluid moves from the brain into the body much like how sewage leaves our homes,” said NINDS’s Daniel S. Reich, M.D., Ph.D. “In this study, we asked the question of what happens once the ‘drain pipes’ leave the ‘house’ — in this case, the brain — and connect up with the city sewer system within the body.” Reich’s group worked jointly with the lab of Jonathan Kipnis, Ph.D., a professor at Washington University in St. Louis.
Reich’s lab used high-resolution magnetic resonance imaging (MRI) to observe the connection between the brain and body’s lymphatic systems in humans. Meanwhile Kipnis’s group was independently using live-cell and other microscopic brain imaging techniques to study these systems in mice.
Using MRI, the researchers scanned the brains of a group of healthy volunteers who had received injections of gadobutrol, a magnetic dye used to visualize disruptions in the blood brain barrier or other kinds of blood vessel damage. Large veins are known to pass through the arachnoid barrier carrying blood away from the brain, and these were clearly observed on the MRI scans. As the scan progressed, a ring of dye appeared around those large veins that slowly spread out over time, suggesting that fluid could make its way through the space around those large veins where they pass through the arachnoid barrier on their way into the dura.
Kipnis’s lab was making similar observations in mice. His group injected mice with light-emitting molecules. Like with the MRI experiments, fluid containing these light-emitting molecules was seen to slip through the arachnoid barrier where blood vessels passed through.
Together, the labs found a “cuff” of cells that surround blood vessels as they pass through the arachnoid space. These areas, which they called arachnoid cuff exit (ACE) points, appear to act as areas where fluid, molecules, and even some cells can pass from the brain into the dura and vice versa, without allowing complete mixing of the two fluids. In some disorders like Alzheimer’s disease, impaired waste clearance can cause disease-causing proteins to build up. Continuing the sewer analogy, Kipnis explained the possible connection to ACE points:
“If your sink is clogged, you can remove water from the sink or fix the faucet, but ultimately you need to fix the drain,” he said. “In the brain, clogs at ACE points may prevent waste from leaving. If we can find a way to clean these clogs, its possible we can protect the brain.”
One implication of ACE points is that they are areas where the immune system can be exposed to and react to changes occurring in the brain. When mice in Dr. Kipnis’s lab were induced to have a disorder where the immune system attacks the myelin in their brain and spinal cord, immune cells could be seen around ACE points and even between the blood vessel wall and the cuff cells; this led over time to a breakdown of the ACE point itself. When the ability of immune cells to interact directly with ACE points was blocked, the severity of infection was reduced.

“The immune system uses molecules to communicate that cross from the brain into the dura mater,” said Kipnis. “This crossing needs to be tightly regulated, otherwise detrimental effects on brain function can occur.”
Reich and his team also observed an interesting connection between the participants’ age and the leakiness of ACE points. In older participants, more dye leaked into the surrounding fluid and space around the blood vessels.
“This might point to a slow breakdown of the ACE points over the course of aging,” said Reich, “and this could be consequential in that the brain and immune system can now interact in ways that they’re not supposed to.”
The connection to aging and the disruption of a barrier separating the brain and immune system fits with what has been observed in aging mice and in autoimmune disorders like multiple sclerosis. This newfound link between the brain and immune system could also help explain why our risk for developing neurodegenerative diseases increases as we get older, but more research is needed to confirm this connection.
This study was supported by the NINDS Intramural Research Program, the National Institute on Aging (AG034113, AG057496, AG078106), and the Cure Alzheimer’s Fund BEE Consortium.

Chronic stress affects the immune system and the brain. UZH researchers now show that a particular enzyme found in cells of the immune system enters the brain under stress. In mice, it causes them to withdraw and avoid social contact. This newly discovered connection between body and mind in stress-related mental illnesses could lead to new treatments for depression.
Chronic stress has far-reaching consequences for our bodies. For example, many stress-related psychiatric illnesses such as depression are associated with changes in the immune system. However, the underlying mechanisms of how these changes affect the brain are still largely unknown.
Enzyme from immune cells in the blood affects nerves in the brain
An international research team led by the University of Zurich (UZH), and the University Hospital of Psychiatry Zurich (PUK) and the Icahn School of Medicine at Mount Sinai, New York, has now uncovered a novel mechanism. “We were able to show that stress increases the amount of the matrix metalloproteinase-8 (MMP-8), an enzyme in the blood of mice. The same changes were found in patients with depression,” says first author Flurin Cathomas. MMP-8 travels from the blood to the brain, where it alters the functioning of certain neurons. In the affected mice, this leads to behavioral changes: they withdraw and avoid social contact.
Potential for new treatments for depression
According to Cathomas, the findings are novel in two respects: “Firstly, they indicate a new ‘body-mind mechanism’, which might be relevant not only for stress-related mental illness, but also for other diseases that affect both the immune and nervous systems.” And secondly, says the psychiatrist, identification of the specific MMP-8 protein could be a potential starting point to develop new treatments for depression.
Changes to brain extracellular matrix
The researchers were able to use animal models to show that stress increases the migration of a specific type of white blood cells called monocytes into the vascular system of the brain, particularly into the reward center regions. These monocytes produce MMP-8. MMP-8 is involved in the restructuring and regulation of the net-like frame that surrounds neurons in the brain — called the extracellular matrix. “If MMP-8 penetrates the brain tissue from the blood, it changes the matrix structure and thus disrupts the functioning of the neurons. Mice who are affected by this process display changes in behavior that are similar to those seen in humans with depression,” says Flurin Cathomas.

In order to prove that MMP-8 was really responsible for the behavioral changes, the researchers removed the MMP-8 gene from some of the mice. Compared to the control mice, these animals did not display stress-related negative behavioral changes. “Blood analyses of patients with depression indicate that the findings from the mouse models are also relevant for humans: both the monocytes and MMP-8 were increased in the blood of people with depression in comparison to healthy participants.”
Clinical studies with patients planned
Many more studies are needed before the results can be implemented in clinical practice. Nevertheless, says Cathomas, “our work once again demonstrates the importance of the interaction between the immune system and the brain in the development of psychiatric disorders. These insights are already being incorporated into psychiatric treatment today.” On the PUK’s special ward for integrative care led by Cathomas, the clinicians take a holistic mind-body approach based on the latest scientific findings when treating their patients.
The research team is now planning clinical studies to investigate the extent to which the immune system can be influenced by stimulating certain areas of the brain. They will also look at whether any changes in the immune system cells of depressive patients influence their behavior.

Whether it’s singing in a choir, playing the living room piano, joining in hymns at church, or just whistling along with the radio, a new poll finds that nearly all older adults say music brings them far more than just entertainment.
Three-quarters of people age 50 to 80 say music helps them relieve stress or relax and 65% say it helps their mental health or mood, according to the new results from the University of Michigan National Poll on Healthy Aging. Meanwhile, 60% say they get energized or motivated by music.
Those are just a few of the health-related benefits cited by older adults who answered questions about listening to and making music of all kinds.
Virtually all (98%) said they benefit in at least one health-related way from engaging with music. In addition, 41% say music is very important to them, with another 48% saying it’s somewhat important.
“Music has the power to bring joy and meaning to life. It is woven into the very fabric of existence for all of humankind,” said Joel Howell, M.D., Ph.D., a professor of internal medicine at the U-M Medical School who worked with the poll team.
Music also has tangible effects on a variety of health-related ailments, he adds. “We know that music is associated with positive effects on measures from blood pressure to depression.”
The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center. The poll team asked a national sample of adults aged 50 to 80 about their experiences with and feelings toward listening to and making music.

Many older adults reported making music with other people at least occasionally, whether by singing or playing an instrument. In all, 8% said they have sung in a choir or other organized group at least a few times in the past year. About 8% of all older adults said they play an instrument with other people at least occasionally.
In all, 46% of older adults reported singing at least a few times a week, and 17% said they play a musical instrument at least a few times a year.
Most respondents reported listening to music, with 85% saying they listen to it at least a few times a week, 80% saying they’ve watched musical performances on television or the internet at least a few times in the past year, and 41% saying they had attended live musical performances in person at least a few times in the past year. That latter percentage was higher among those with higher incomes and more education.
The poll shows other differences between groups in music listening habits and health impacts.
Those who said their physical health is fair or poor, and those who say they often feel isolated, were less likely to listen to music every day. Black older adults were more likely than others to have sung in a choir in the past year, and Black and Hispanic older adults were more likely to say that music is very important to them.
“While music doesn’t come up often in older adults’ visits with their usual care providers, perhaps it should,” said poll director Jeffrey Kullgren, M.D., M.P.H., M.S. “The power of music to connect us, improve mood and energy, or even ease pain (like 7% of respondents said it does for them), means it could be a powerful tool.” Kullgren is a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Howell notes that music helps people keep in touch with one another throughout their lifetime. Indeed, 19% of the poll respondents said music is even more important to them now than it was in their youth, and 46% said it’s just as important to them now as then.
With the rising concern about the health effects of loneliness and social isolation among Americans in general, and especially among older adults, the power of music to connect people and support healthy aging should not be underestimated, Howell says. The NPHA has previously reported on trends in loneliness and social isolation in older adults.
“Music is a universal language that has powerful potential to improve wellbeing,” said Sarah Lenz Lock, senior vice president of Policy and Brain Health at AARP and executive director of the Global Council on Brain Health. “AARP’s own research shows that music can play an important role in healthy aging by improving our moods, fostering social connections and, potentially, enriching our brain health.”
The poll report is based on findings from a nationally representative survey conducted by NORC at the University of Chicago for IHPI and administered online and via phone in July and August 2023 among 2,657 adults aged 50 to 80. The sample was subsequently weighted to reflect the U.S. population. Read past National Poll on Healthy Aging reports and about the poll methodology.

With all of the fantastic imaging techniques available in healthcare today, clinicians are capable of diagnosing tissue and joint deformities using non-invasive imaging with remarkable accuracy. However, one vexing question remains: why are some patients with specific joint deformities symptomatic while others are not?
The meniscus is a piece of cartilage that cushions the knee joint between the femur (thigh bone) and the tibia (shin bone). Some people are born with a congenital morphological variation in their meniscus, called a discoid lateral meniscus (DLM), where the meniscus is thickened on the lateral, or outer side of the knee. DLM malformations cause the lateral meniscus to form a circle rather than a crescent shape, thickening the cartilage and making it more prone to tears. Some patients develop symptoms such as knee pain and a locking, leading to surgery.
In order to better understand what factors separate symptomatic DLM cases from asymptomatic cases, a multi-institutional team of researchers led by Dr. Kazuya Nishino of the Graduate School of Medicine at Osaka Metropolitan University analyzed 61 knees with discoid lateral meniscus surgery without dislocation (symptomatic group) and 35 without symptoms but with discoid lateral meniscus detected on MRI (asymptomatic group). The percentage of meniscus was calculated in the coronal and sagittal sections, respectively. The researchers also measured the height of the thinnest and thickest part of the meniscus.
The results revealed that the percentage of the meniscus covering the tibia in the coronal and sagittal planes was higher in the symptomatic group than in the asymptomatic group. Additionally, the results showed that the meniscal height was greater in the symptomatic group than in the asymptomatic group.
Overall, preoperative imaging is helpful in determining the amount of tissue resection, or removal, required for patients with symptomatic DLM. “Making surgical decisions and plans based on these characteristics is expected to assist in medical treatment. In the future, we will investigate the morphological changes of the meniscus before and after surgery in three dimensions,” said Dr. Nishino.
While the difference in the morphologies of symptomatic vs. asymptomatic DLMs was the most important finding in the study, the MRIs of symptomatic patients also showed meniscal tears or other evidence of instability. The researchers suggest that these morphological features could be responsible for DLM symptoms in symptomatic patients.

A new study suggests a naturally-occurring material is an effective disinfectant for contact lenses, worn by millions of people worldwide.
Microbial keratitis is one of the most serious potential complications for contact lens wearers. It’s an infection of the cornea that is caused by bacteria; the most common being Pseudomonas aeruginosa.
Previous studies have found that existing disinfecting solutions are not effective for preventing biofilm, which are clusters of bacteria that attach to the surface of lenses.
Hydroquinine, an organic compound found in the bark of some trees, is known to have bacterial killing activity against Pseudomonas aeruginosa and several other clinically important germs, including Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.
The team behind the discovery, from the University of Portsmouth in England and Naresuan and Pibulsongkram Rajabhat universities in Thailand, has now explored the potential use of multipurpose formulas containing hydroquinine as a disinfectant for contact lenses.
They examined the antibacterial, anti-adhesion, and anti-biofilm properties of hydroquinine-formulated multi-purpose solutions (MPSs), and then compared it to two commercial MPSs; Opti-free Replenish and Q-eye. The natural compound killed 99.9 per cent of bacteria at the time of disinfection.
The paper, published in Antibiotics, says these findings may aid in the development of novel disinfectants aimed at combating the P. aeruginosa bacteria.

Dr Robert Baldock from the School of Pharmacy and Biomedical Sciences at the University of Portsmouth, said: “Commercially available disinfecting solutions, which are made up of a number of chemicals, can sometimes cause reactions with painful side-effects.
“We hoped to demonstrate that new agents made from natural products may be an excellent option to limit or reduce the risk of contact lens contamination.
“It is exciting to see how this research has progressed; from discovery to exploring potential applications.”
There are up to 3.5 million reports of corneal infections annually, and in extreme cases it can result in permanent eye damage and vision loss. The risk of microbial keratitis doubles when someone wears contact lenses overnight and or longer than the recommended daily amount.
Corneal blindness resulting from microbial keratitis is emerging as a prominent cause of visual disability, according to the World Health Organisation (WHO). The World Health Organisation (WHO) has also classified multidrug-resistant P. aeruginosa as one of the most concerning pathogens.
Drug-resistant bacteria occur in more than 2.8 million infections and are responsible for 35,000 deaths per year. Antimicrobial resistance happens when germs change over time and no longer respond to medicines, making it difficult to treat infections.

Amoxicillin and Trimethoprim are commonly prescribed antibiotics that certain strains of P. aeruginosa have become resistant to.
Hydroquinine is already known to be an effective agent against malaria in humans, and it is also being used in the Netherlands to treat nocturnal muscle cramps. Until now, there has been little investigation into its drug-resistant properties.
Lead author, Sattaporn Weawsiangsang from the Faculty Of Allied Health Sciences at Naresuan University, is currently a visiting researcher at the University of Portsmouth.
She said: “Our initial findings suggest that soaking contact lenses in a multi-purpose solution containing hydroquinine is possibly helpful to prevent contamination and infection.
“However, further investigation is needed to determine whether hydroquinine itself also has adverse reactions or toxicity.
“We are continuing to test the compound on a number of cells, and so far, the results are really promising. This potential development could contribute to the creation of new disinfectants from natural products, effectively combating P. aeruginosa infections and reducing cases of corneal infections.”
The paper concludes by recommending further research examining the effectiveness of hydroquinine with several different contact lens materials, and against other pathogenic microorganisms.

The human brain is an organ that takes nearly from 20 to 25% of the energy the body needs. This high energy demand for neuronal functions depends on the transport and precise distribution of mitochondria — the energy-generating cell organelles — in each neuron. Now, a study published in the journal Science Signaling has identified, for the first time, a molecular complex that regulates the transport of mitochondria within neurons and neuronal death. The discovery of the complex, exclusively present in the most evolved mammals, could help to locate new therapeutic targets against neurodegenerative diseases such as Parkinson’s, neuromuscular diseases or even some types of tumours.
The study, conducted on animal models and cell cultures, is led by Professor Eduardo Soriano, from the University of Barcelona and the Institute of Neurosciences of the UB (UBneuro), and the Biomedical Research Networking Centre on Neurodegenerative Diseases (CIBERNED), and researcher Anna María Aragay, member of the Spanish National Research Council (CSIC) and the Institute of Molecular Biology of Barcelona (IBMB-CSIC).
The article, whose first authors are Ismael Izquierdo-Villalba (IBMB-CSIC), Serena Mirra and Yasmina Manso (UB-CIBERNED), includes the participation of Adolfo López de Munain, from the University Hospital of Donostia, Xavier Navarro, from the Autonomous University of Barcelona (UAB), both members of CIBERNED, and José Antonio Enríquez, collaborator at the Biomedical Networking Research on Fragility and Healthy Ageing (CIBERFES) and the National Centre of Cardiovascular Research Carlos III (CNIC).
Bringing energy for neuronal functions
“In neurons, the transport process of mitochondria is determining, since these organelles must be present along all axons and dendrites — neuron extensions — to provide energy to the neurotransmission and the neuronal functions, processes that require a lot of energy. This great consumption depends on a specific and precise distribution of mitochondria within neurons,” notes Soriano, co-director of the study and member of the Department of Cell Biology, Physiology and Immunology at the UB’s Faculty of Biology.
The study reveals the Alex3/Gαq mitochondrial complex interacts with the mitochondria machinery to distribute and transport these cell organelles along the neurons’ axons and dendrite. This process depends on the interaction of the Gq protein with the Alex3 mitochondrial protein.
“For the first time, we found that the Alex3/Gαq is essential not only for the transport and mitochondrial function, but also for neuronal physiology, movement control and neuronal viability. If this system is inactivated — for instance, in mice with a specific deficiency of the Alex3 protein in the central nervous system — the mitochondrial trafficking is reduced, there is less dendritic and axonal arborizations and this causes motor deficits and even neuronal death,” says Aragay, co-director of the study.

The authors of the study had previously described in other articles that the Alex3 and Gαq proteins regulated mitochondrial transport. However, they did not know how these interacted or what molecular mechanisms took part in the process.
The interaction of the Alex3/Gαq mitochondrial complex is regulated through the G protein-coupled receptors (GPCR), according to the study. These receptors have many molecules — neurotransmitters, hormones, cannabinoids, etc. — with different functions in the organism.
“The activation of GPCRs not only alters the mitochondrial distribution but also its function, and as a notable effect, the neuronal growth and viability. Our study suggests that, in general, these molecules that interact with these receptors could regulate several aspects of the mitochondrial biology through the GPCR,” note the experts.
Controlling receptors to fight human diseases
Although the action mechanisms are not well known yet, it seems that different functions played by the Alex3 protein could be associated with many pathologies. For instance, it appears that deletions — loss of a DNA fragment — of the Alex3 facilitate the development of certain tumours (epithelial cancers). In other cases, the deletion or inhibition of its expression has a protective effect on certain tumours (liver cancers).
Apart from its association with cancer, some genic variants of the Alex3 protein and its genic family are also related to neurodegenerative diseases — especially Parkinson’s — , sleep apnoea and metabolic diseases.
“The fact that inactivating mutations have not been identified in the databanks of thousands of human genomes would indicate that the Alex3 gene has a relevant function. Its total loss is not viable in the organism, and it would be found as a somatic mutation in tumours,” says Professor Gemma Marfany, co-author of the study and member of the UB’s Department of Genetics, Microbiology and Statistics, the Institute of Biomedicine of the UB (IBUB) and the Rare Diseases Networking Biomedical Research Centre (CIBERER).
“Moreover, mutations in the gene that codes for Gαq in humans lead to motor disorders, cognitive deficits, intellectual disability and epilepsy,” notes Aragay. The authors highlight that these data show the relevance of the identified complex for neuronal function.
“Being able to control mitochondrial biology from outside the cell via GPCR receptors is a great advantage. Currently, many specific molecules activate or inhibit these receptors, so it is important to explore the possibility of controlling the localization and biology of mitochondria in diseases where there is a deficit of these organelles (e.g. mitochondrial or neuromuscular diseases), or in pathologies where inhibition of metabolism has positive therapeutic effects (e.g. cancer),” the team concludes.

A major challenge to developing better neural prostheses is sensory encoding: transforming information captured from the environment by sensors into neural signals that can be interpreted by the nervous system. But because the number of electrodes in a prosthesis is limited, this environmental input must be reduced in some way, while still preserving the quality of the data that is transmitted to the brain.
Demetri Psaltis (Optics Lab) and Christophe Moser (Laboratory of Applied Photonics Devices) collaborated with Diego Ghezzi of the Hôpital ophtalmique Jules-Gonin — Fondation Asile des Aveugles (previously Medtronic Chair in Neuroengineering at EPFL) to apply machine learning to the problem of compressing image data with multiple dimensions, such as color, contrast, etc. In their case, the compression goal was downsampling, or reducing the number of pixels of an image to be transmitted via a retinal prosthesis.
“Downsampling for retinal implants is currently done by pixel averaging, which is essentially what graphics software does when you want to reduce a file size. But at the end of the day, this is a mathematical process; there is no learning involved,” Ghezzi explains.
“We found that if we applied a learning-based approach, we got improved results in terms of optimized sensory encoding. But more surprising was that when we used an unconstrained neural network, it learned to mimic aspects of retinal processing on its own.”
Specifically, the researchers’ machine learning approach, called an actor-model framework, was especially good at finding a “sweet spot” for image contrast. Ghezzi uses Photoshop as an example. “If you move the contrast slider too far in one or the other direction, the image becomes harder to see. Our network evolved filters to reproduce some of the characteristics of retinal processing.”
The results have recently been published in Nature Communications.
Validation both in-silico and ex-vivo
In the actor-model framework, two neural networks work in a complementary fashion. The model portion, or forward model, acts as a digital twin of the retina: it is first trained to receive a high-resolution image and output a binary neural code that is as similar as possible to the neural code generated by a biological retina. The actor network is then trained to downsample a high-resolution image that can elicit a neural code from the forward model that is as close as possible to that produced by the biological retina in response to the original image.

Using this framework, the researchers tested downsampled images on both the retina digital twin and on mouse cadaver retinas that had been removed (explanted) and placed in a culture medium. Both experiments revealed that the actor-model approach produced images eliciting a neuronal response more akin to the original image response than an image generated by a learning-free computation approach, such as pixel-averaging.
Despite the methodological and ethical challenges involved in using explanted mouse retinas, Ghezzi says that it was this ex-vivo validation of their model that makes their study a true innovation in the field.
“We cannot only trust the digital, or in-silico, model. This is why we did these experiments — to validate our approach.”
Other sensory horizons
Because the team has past experience working on retinal prostheses, this was their first use of the actor-model framework for sensory encoding. But Ghezzi sees potential to expand the framework’s applications within and beyond the realm of vision restoration. He adds that it will be important to determine how much of the model, which was validated using mice retinas, is applicable to humans.
“The obvious next step is to see how can we compress an image more broadly, beyond pixel reduction, so that the framework can play with multiple visual dimensions at the same time. Another possibility is to transpose this retinal model to outputs from other regions of the brain. It could even potentially be linked to other devices, like auditory or limb prostheses,” Ghezzi says.

Approximately ten per cent of the world’s population currently suffers from chronic kidney disease (CKD). This puts people at increased risk of kidney failure, cardiovascular disease and hospitalisation — and places a heavy burden on the healthcare system. Due to the demographic changes of an ageing population, it is predicted that CKD could become one of the five leading causes of death worldwide by 2040.
In a large-scale study, scientists from Leipzig University, in collaboration with other international study groups, investigated genetic associations between variants of the X chromosome and seven selected parameters of kidney function in men and women. The study was based on blood samples and genetic information from a total of more than 900,000 people, 80 per cent of whom were of European descent.
“We identified a total of 23 associations: 16 relate to the estimated glomerular filtration rate of the kidney and seven to uric acid,” explains study leader Professor Markus Scholz from the Institute for Medical Informatics, Statistics and Epidemiology (IMISE) at Leipzig University. Along with uric acid, glomerular filtration rate is a key measure of kidney health. It shows how much blood the glomeruli — small vessels in the kidney tissue — can filter per unit of time.
The researchers found different effects in men and women at six positions in the genome. The scientists were able to assign functionally plausible candidate genes to the newly discovered genetic effects. “The sex-specific differences could be explained by hormonal regulation of the associated genes,” reports study analyst Katrin Horn from IMISE. “This finding helps us to better understand possible mechanisms of disease development and progression,” says Professor Markus Scholz: “For example, we already know that the disease is more common in women, but progresses faster in men. We now have suitable mechanisms to investigate these phenomena further.”
In their analysis of X-chromosomal variants, the Leipzig scientists looked at mutations at around 270,000 positions on the chromosome and correlated these with the clinical kidney parameters. They also used tissue data to check whether and how the genetic information was actually used. A targeted search for differences between the sexes was carried out.
“We deliberately chose to analyse the more complicated X chromosome, which has not yet been sufficiently investigated in terms of genetic associations despite being very promising with regard to sex-specific differences in diseases,” says bioinformatics researcher Professor Scholz. “The reason for this is that women have two of these chromosomes, but the genetic information is only partially utilised and it is not exactly understood in what way and to what extent this happens.”
The method that Professor Scholz and his team have developed for this study to analyse the X chromosome in detail and identify sex-specific differences can also be used by other research teams in the future to contribute to sex-sensitive medicine for other diseases.
The study was part of the international CKDGen consortium for research into the genetics of kidney disease, which is led by Professor Anna Köttgen of the University of Freiburg, with Leipzig University as a key partner. It included data from the Leipzig studies LIFE Heart, LIFE Adult, LIFE Child and the Sorb Study, from a total of approximately 14,000 data records. The bulk of the analysis and interpretation of the data was carried out by Professor Scholz’s research group.

The ability to detect diseases at an early stage or even predict their onset would be of tremendous benefit to doctors and patients alike. A research team led by Dr. Larysa Baraban at the at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) develops intelligent, miniaturized biosensor devices and systems using nanomaterials to determine biomolecules and cells as well as biochemical reactions or processes as disease markers. The team’s current publication in Biosensors and Bioelectronics describes the development of a portable, palm-sized test system that can simultaneously carry out up to thirty-two analyses of one sample.
Various possibilities and mechanisms exist for detecting pathogens in body fluids. One option that Baraban investigates at the HZDR-Institute of Radiopharmaceutical Cancer Research is the detection using field-effect transistors (FETs) from the realm of electronics. The operating principle is simple: a defined electrical current flows from A to B. This current can be regulated by the electrical potential on the surface of a gate, which functions like a precise, continuous valve. Disease-relevant biomolecules bind to the gate surface and thereby change the electrical potential and therefore the current as well. If there is no significant change in the current, no biomolecules have bound to the sensor surface. On the other hand, a change in the current means that disease-related molecules can be detected on the sensor surface. These biosensors can be designed to specifically detect different biomolecules. Different pathogens cause different electrical potentials and therefore different currents. Cancer cells cause different current than, for example, a flu virus.
Development of reusable transistors
The major disadvantage of traditional electronic FET-based biosensors is that the test surfaces are not reusable, and the entire transistor must be discarded after each sampling. As transistors contain costly semiconductor materials, this process is both expensive and harmful to the environment. For that reason, Baraban and her Department of Nano-Microsystems for Life Sciences went one step further and attempted to measure the potential changes not directly on the surface of the transistor, but on a separate electrode that is connected to the transistor’s gate. “This allows us the opportunity to use the transistor multiple times. We separate the gate and refer to it as an ‘extended gate’ — that is, an extension of the test system.”
But that’s not all. The team thought even further ahead and took on another challenge: “We, of course, would like this system to carry out several analyses at the same time.” The researchers succeeded in developing extended gates with thirty-two test pads. Baraban explains, “This means that a sample can be tested simultaneously on each of the pads for a different pathogen.”
The scientists first demonstrated the operating principle using interleukin-6 (IL-6), a molecule responsible for communication between immune cells. “Whether it’s a simple cold or cancer, the concentration of IL-6 changes. Different diseases as well as different stages of a disease produce different clinical pictures. That is why IL-6 is very well suited as a marker.”
Nanoparticles to increase sensitivity
In order to make the method even more sensitive, Baraban’s team also utilized nanostructures. Nanoparticles concentrate or localize the charge to amplify the voltage signal. “The sensitivity of the tests is considerably higher than when we work without nanoparticles.” As ready-made nanoparticle kits for research are now available on the market, this method is simple to use. The HZDR scientists are currently working with gold nanoparticles. In the future, they would also like to study other nanoparticles.
As a result of the current research, a functional, handy test system has been created, consisting of a transistor and thirty-two test pads, with which different pathogens can be detected in a very short period of time. In the future, the described test system could, for example, be used to monitor the progress of immunotherapies in cancer patients. Another possibility would be to predict the severity and course of a viral disease such as the flu or COVID-19 at the very onset. In comparison to existing technologies, the new system is more cost-effective and faster. For that reason, Baraban and her team are now hoping for interest from the commercial sector.

A new study finds there are simple activities that can help people improve their mood and emotional well-being on a day-to-day basis after the traumatic loss of a loved one.
“The untimely or traumatic death of close friends or family is emotionally taxing, and navigating grief can be difficult,” says Caitlin Reynolds, co-author of the study and a Ph.D. student at North Carolina State University. “Our study suggests there are specific things people can do to bolster their emotional well-being following a traumatic loss.”
“We were conducting a larger study that looked at how daily behaviors affect emotional well-being and day-to-day functioning, and we realized that a significant number of study participants were dealing with the traumatic loss of a loved one,” says Shevaun Neupert, corresponding author of the study and a professor of psychology at NC State. “This gave us an opportunity to gain insights into how daily behaviors in the wake of a loss can influence our emotional well-being.”
For the study, researchers worked with data from 440 U.S. adults between the ages of 50 and 85. 356 of the study participants reported the traumatic loss of a loved one. Study participants completed a daily diary survey for 14 consecutive days. The survey questions were designed to capture changes in each participant’s day-to-day lived experiences and “affect” — or mood.
“The survey questions also helped us capture information related to subjective age, or how old people report feeling each day,” Neupert says. “Do they feel older than they actually are? Younger? And how does that correlate to their mood or emotional well-being?”
“One of the study’s big findings is that activities we call ‘uplifts’ can have a significant impact,” says Ali Early, co-author of the study and a former undergraduate at NC State.
Uplifts refer to a variety of activities that can improve our mood, such as: Completing a task; Getting enough sleep; Dining out; Visiting, phoning or writing a friend; or Spending time with family.”Uplifts were good for everyone, but there is some nuance in not only who is most impacted, but when the uplifts are most powerful,” Neupert says. “For example, we found that the positive effect of uplifts was more pronounced for people who had experienced traumatic loss, and especially so on days when they reported feeling older.”

The findings held true even when researchers accounted for the socioeconomic status of study participants, their age and the age at which they first experienced a traumatic loss.
“In other words, there are things we can do — which are accessible for most people — to improve our moods,” Neupert says. “And those things can help us most on days when we most need it.”
The paper, “Traumatic Losses Permeate Daily Emotional Experiences: Roles of Daily Uplifts and Subjective Age,” is published open access in the journal Applied Psychology: Health and Well-Being.