Scientists discover potential treatment approaches for polycystic kidney disease

cientists would like to know how cysts form in polycystic kidney disease (PKD). Here, they compared two 3-D mini-kidney models. On the left, a model shows a mini kidney with a gene mutation that causes cysts to form. On the right, researchers used gene editing to correct a gene mutation, preventing the development of cysts.
Image Credit: Vishy, et al., Cell Stem Cell 2024

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide. The study, partially funded by the National Institutes of Health (NIH), is published in Cell Stem Cell.

Scientists used gene editing and 3-D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

“Human PKD has been so difficult to study because cysts take years and decades to form,” said senior study author Benjamin Freedman, Ph.D., at the University of Washington, Seattle. “This new platform finally gives us a model to study the genetics of the disease and hopefully start to provide answers to the millions affected by this disease.”

The Rotisserie-Inspired Device That Could Revolutionize Cancer Surgery

The Zavaleta Lab’S Raman Rotisserie Device Creates a Map of the Surface of a Resected Tumor to Aid Surgeons in the Operating Room.
Photo Credit: Alex Czaja

Like many Texans, Cristina Zavaleta grew up enjoying the culinary delights of the state’s famous smokehouse BBQs. She couldn’t have imagined that those humble rotisseries of her childhood would one day inspire a game-changing device for the operating room that could help surgeons prevent tumor recurrence.

On a team excursion to Disneyland, the WiSE Gabilan Assistant Professor of Biomedical Engineering and her students were reminded of rotisseries when they encountered a food vendor at the Star Wars-themed land, Galaxy’s Edge. It was a lightbulb moment. The rotisserie configuration was a perfect way of intricately scanning excised tumors, with the help of the Zaveleta Lab’s unique nanoparticles, to light up where the cancerous tissue may not have been entirely removed from the patient. Surgeons could then be guided to precisely remove the remaining tumor, all while the patient is still under anesthesia. The result would reduce the need for traumatic repeat surgeries and potential cancer recurrence and metastasis.

Zavaleta and her team built the device, which they dubbed the Raman Rotisserie. It physically rotates a tumor specimen and works in conjunction with an imaging technique known as Raman spectroscopy, which scans the surface of the excised tumor. Their research, which aims to improve the success rate of breast cancer lumpectomies, has now been published in NPJ Imaging.

Feeding the lonely brain

Study finds that lonely women experienced increased activation in regions of the brain associated with food cravings
Photo Credit: Ryanwar Hanif

A new UCLA Health study has found that women who perceive themselves to be lonely exhibited activity in regions of the brain associated with cravings and motivation towards eating especially when shown pictures of high calorie foods such as sugary foods. The same group of women also had unhealthy eating behaviors and poor mental health.

Arpana Gupta, Ph.D., a researcher and co-director of the UCLA Goodman-Luskin Microbiome Center, wanted to research the negative impacts of loneliness, especially as people continue to be working remotely after the COVID-19 pandemic, and how the brain interplays with social isolation, eating habits, and mental health. While it is established that obesity is linked to depression and anxiety, and that binge eating is understood to be a coping mechanism against loneliness, Gupta wanted to observe the brain pathways associated with these feelings and behaviors.

“Researching how the brain processes loneliness and how this is related to obesity and health outcomes hasn't been done,” said Gupta, senior author of the paper, which is published in JAMA Network Open. 

The researchers surveyed 93 women about their support system and their feelings of loneliness and isolation, then separated them into two groups: those who scored high on the perceived social isolation scale, and those who scored low. The researchers found that women who had higher levels of social isolation tended to have higher fat mass, lower diet quality, greater cravings, reward-based eating, and uncontrolled eating, and increased levels of anxiety and depression.

Vaping additives harm a vital membrane in the lungs, according to new Concordia research

Panagiota Taktikakis (left) and Christine DeWolf: “Understanding the impact of vaping additives on lung surfactant is vital, particularly for younger generations who are more influenced by vaping trends.”
Photo Credit: Courtesy of Concordia University

The health risks associated with consumption of tobacco and cannabis products are well-established by now. Much less understood are the risks associated with vaping, particularly flavored products popular with young adults.

It is an increasingly pressing issue: Statistics Canada says one in 10 Canadians aged 20 to 24 and one in 15 aged 15 to 19 reported to have vaped every day in 2022.

Writing in the journal Langmuir, Concordia researchers show how the e-cigarette additive tocopherol — an organic compound better known as vitamin E — and tocopherol acetate can damage the lungs. The study adds to the growing body of literature on what has become known as electronic cigarette or vaping product use–associated lung injury (EVALI).

When heated and inhaled, the compound embeds in the pulmonary surfactant, a nanoscopically thin lipid protein membrane coating the surface of the alveoli that regulates the oxygen-carbon dioxide gas exchange and stabilizes the lungs’ surface tension during breathing.

Scientists identify rare gene variants which confer up to 6-fold increase in risk of obesity

Photo Credit: Mart Production

The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

The study, published in Nature Genetics, was led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the University of Cambridge.

The researchers used UK Biobank and other data to perform whole exome sequencing of body mass index (BMI) in over 500,000 individuals.

They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity as much as six times and was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes.

The Bassoon gene variants were found to affect 1 in 6,500 adults, so could affect about 10,000 people in the UK.

“It’s ultimately about predicting everything” – theory could be a map to hunted quantum materials

Photo Credit: Vendi Jukic Buca

A breakthrough in theoretical physics is an important step towards predicting the behavior of the fundamental matter of which our world is built. It can be used to calculate systems of enormous quantities of quantum particles, a feat thought impossible before. The University of Copenhagen research may prove of great importance for the design of quantum computers and could even be a map to superconductors that function at room-temperature.

On the fringes of theoretical physics, Berislav Buca investigates the nearly impossible by way of "exotic" mathematics. His latest theory is no exception. By making it possible to calculate the dynamics, i.e., movements and interactions, of systems with enormous quantities of quantum particles, it has delivered something that had been written off in physics. An impossibility made possible.

The unexpected presence of a white cat adorns the illustrations of Buca's research. Pulci the cat is his eye-catching muse. Arrows through the cat's body illustrate the quantum mechanical origin of the playful cat's movements – and this is precisely the relationship that Buca is trying to understand by making it possible to calculate the dynamics of the very smallest particles.

The breakthrough has reinvigorated an old and fundamental scientific question: Theoretically, if all behavior in the universe can be calculated by way of the laws of physics, can we then predict everything by calculating its smallest particles? 

Heat flows the secret to order in prebiotic molecular kitchen

Schematic visualization of heat flows in rock cracks.
Illustration Credit: Christof Mast

Life is complicated. What is true for our everyday existence also holds for the many complex processes that take place inside cells. Proteins constantly have to be synthesized, cell walls built, and DNA replicated. This can only work when reaction partners converge at the right time in sufficiently high concentrations while suffering little disruption from other substances. Over the course of billions of years, evolution has perfected these mechanisms and ensured that such vital processes occur with high efficiency at the correct place.

Circumstances were probably a lot more chaotic four billion years ago, when prebiotic reactions created the conditions for the emergence of the first lifeforms. For these reactions, too, it was necessary for the ‘right’ substances to be brought together at the ‘right’ time in one place, so that more complex biomolecules like RNA and amino acid chains could form. While such reactions are possible to recreate in the laboratory thanks to manual intermediate steps, it is highly challenging for them to come about in a simple ‘primordial soup’ – that is to say, a very dilute mixture of prebiotic building blocks. So how could nature create suitable conditions for the origin of life?

Shy sea anemones are more likely to survive heatwaves

Photo Credit: Praveen Kenderla

Even in nature, pride can prevail. A study with researchers from the University of Gothenburg shows that sea anemones that react more slowly to change can survive a heatwave better than individuals that change their behavior quickly.

Along the Atlantic coasts of Europe, many species are exposed to abrupt shifts in habitat. Tides, storms and rapid temperature changes are commonplace for the marine species that live there. With climate change, heatwaves are expected to become more frequent, and researchers wanted to find out how coastal marine species cope with extreme water temperatures. They chose to study the sea anemone species Actinia equina, a species that exhibits individual behaviors.

Bold or shy

“We call them animal personalities. They are different behavioral life strategies found in the same species. The anemones we studied have two personality traits, bold and shy, and in extreme heat waves the shy anemones do better,” says Lynne Sneddon, a zoophysiologist at the University of Gothenburg and co-author of the study published in the Journal of Experimental Biology.

Physics of Complex Fluids: Ring Polymers Show Unexpected Motion Patterns Under Shear

Schematic of poly[2]catenane slip tumbling and bonded ring gradient tumbling.
Illustration Credit: Reyhaneh A. Farimani

An international research team is attracting the attention of experts in the field with computational results on the behavior of ring polymers under shear forces: Reyhaneh Farimani, University of Vienna, and her colleagues showed that for the simplest case of connected ring pairs, the type of linkage – chemically bonded vs. mechanically linked – has profound effects on the dynamic properties under continuous shear. In these cases, novel rheological patterns emerge. In addition to being recently published in the prestigious journal Physical Review Letters, the study received an "Editors' Suggestion" for its particular novelty.

The shearing of fluids – meaning the sliding of fluid layers over each other under shear forces – is an important concept in nature and in rheology, the science that studies the flow behavior of matter, including liquids and soft solids. Shear forces are lateral forces applied parallel to a material, inducing deformation or slippage between its layers. Fluid shear experiments allow the characterization of important rheological properties such as viscosity (resistance to deformation or flow) and thixotropy (decrease in viscosity under the influence of shear) which are important in applications ranging from industrial processes to medicine. Studies on the shear behavior of viscoelastic fluids, created by introducing polymers into Newtonian fluids, have already been conducted in recent years. However, a novel approach in the current research involves the consideration of polymer topology – the spatial arrangement and structure of molecules – by using ring polymers. Ring polymers are macromolecules composed of repeating units, forming closed loops without free ends. 

Autism and ADHD are linked to disturbed gut flora very early in life

The researchers have found links between the gut flora in babies first year of life and future diagnoses.
Photo Credit: Cheryl Holt

Disturbed gut flora during the first years of life is associated with diagnoses such as autism and ADHD later in life. This is according to a study led by researchers at the University of Florida and Linköping University and published in the journal Cell.

The study is the first forward-looking, or prospective, study to examine gut flora composition and a large variety of other factors in infants, in relation to the development of the children's nervous system. The researchers have found many biological markers that seem to be associated with future neurological development disorders, such as autism spectrum disorder, ADHD, communication disorder and intellectual disability.

“The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis,” says Eric W Triplett, professor at the Department of Microbiology and Cell Science at the University of Florida, USA, one of the researchers who led the study.

Discovery of how COVID-19 virus replicates opens door to new antiviral therapies

A new study, looking at the replication stage of the SARS-CoV-2 virus that causes COVID-19, discovered important mechanisms in its replication that could be the foundation for new antiviral therapies.
Image Credit: Gerd Altmann

The study, which sets out to investigate how the SARS-CoV-2 virus replicates once it enters the cells, has made surprising discoveries that could be the foundation for future antiviral therapies. It also has important theoretical implications as the replication of the SARS-CoV-2 virus has, so far, received less attention from researchers.

The viral life cycle can be broken down into two main stages: the first stage is where the virus enters the cell. The second stage is replication where the virus uses the molecular machinery of the cell it has infected to replicate itself by building its parts, assembling them into new viruses that can then exit to infect other cells.

The majority of research into SARS-CoV-2 – the causative agent of COVID-19 – has focused on the Spike protein that allows viral entry. This has led to a lack of understanding of how the virus replicates once it has entered the cell.

A new paper led by Dr Jeremy Carlton in collaboration with Dr David Bauer at the Francis Crick Institute, focuses on how the Envelope protein of SARS-CoV-2 controls late stages of viral replication.

Self-assembly of complex systems: hexagonal building blocks are better

Professor Erwin Frey
Photo Credit: © Benjamin Asher / Ludwig-Maximilians-Universität München

Complex systems in nature, like their synthetic counterparts in technology, comprise a large number of small components that assemble of their own accord through molecular interactions. Gaining a better understanding of the principles and mechanisms of this self-assembly is important for the development of new applications in domains such as nanotechnology and medicine.

Professor Erwin Frey, Chair of Statistical and Biological Physics at LMU and member of the ORIGINS Excellence Cluster, and his research fellow Dr. Florian Gartner has now investigated an aspect of self-assembly that has received little attention before now: What role do the shape and the number of possible bonds between particles play? As the researchers report in the journal Physical Review X, their results show that hexagonal morphologies – in other words, six-sided structures – such as molecules with six binding sites are ideal for self-assembly.

Drug shows promise for slowing progression of rare, painful genetic disease

A CT angiography scan of a person with ACDC disease showing abnormal calcification of the blood vessels in the legs and feet.
Image Credit: Courtesy of National Institutes of Health

A drug used to treat certain bone diseases shows promise for slowing the progression of a rare, painful genetic condition that causes excessive calcium buildup in the arteries, known as arterial calcification due to deficiency of CD73 (ACDC). These results are from a first-in-human clinical trial supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study, published in the journal Vascular Medicine, could lead to the first effective treatment for the rare disease.

ACDC, which has no known cure, often targets the arteries of the legs and can make walking painful and difficult. It can also affect the joints of the hands, causing pain and deformities. In severe cases, the condition can lead to potential limb loss. Symptoms of the disease often begin in the late teens and 20s. An extremely rare disease, it is believed to affect only about 20 people worldwide and has an estimated prevalence of less than 1 in 1 million. Previous studies have identified the gene for ACDC disease and the biochemical mechanism behind it. More recent studies by the NHLBI research team identified an existing drug, called etidronate, as a potential treatment for ACDC based on disease models in animals and human cells.

Pressure determines which embryonic cells become ‘organizers’

 Tooth epithelium (cell surface; yellow) and mesenchyme (cell surface; magenta). Proliferating cells (cyan) expand the tissue, generating a mechanical pressure at the tissue center that drives the formation of the main tooth signaling center or organizer, the enamel knot.
Photo Credit Neha Pincha Shroff and Pengfei Xu

A collaboration between research groups at the University of California, TU Dresden in Germany and Cedars-Sinai Guerin Children’s in Los Angeles has identified a mechanism by which embryonic cells organize themselves to send signals to surrounding cells, telling them where to go and what to do. While these signaling centers have been known to science for a while, how individual cells turn into organizers has been something of a mystery.

Until now. In a paper published in the journal Nature Cell Biology, the researchers find that cells are literally pressed into becoming organizers.

“We were able to use microdroplet techniques to figure out how the buildup of mechanical pressure affects organ formation,” said co-corresponding author Otger Campàs, former associate professor of mechanical engineering at UC Santa Barbara, who is currently managing director, professor and chair of tissue dynamics at the Physics of Life Excellence Cluster of TU Dresden.

Discovery could end global amphibian pandemic

Panamanian golden frog
Photo Credit: Brian Gratwicke/U.S. Fish & Wildlife Service

A fungus devastating frogs and toads on nearly every continent may have an Achilles heel. Scientists have discovered a virus that infects the fungus, and that could be engineered to save the amphibians.

The fungus, Batrachochytrium dendrobatidis or Bd, ravages the skin of frogs and toads, and eventually causes heart failure. To date it has contributed to the decline of over 500 amphibian species, and 90 possible extinctions including yellow-legged mountain frogs in the Sierras and the Panamanian golden frog. 

A new paper in the journal Current Biology documents the discovery of a virus that infects Bd, and which could be engineered to control the fungal disease.

The UC Riverside researchers who found the virus are excited about the implications of their discovery. In addition to helping them learn about how fungal pathogens rise and spread, it offers the hope of ending what they call a global amphibian pandemic. 

“Frogs control bad insects, crop pests, and mosquitoes. If their populations all over the world collapse, it could be devastating,” said UCR microbiology doctoral student and paper author Mark Yacoub. 

“They’re also the canary in the coal mine of climate change. As temperatures get warmer, UV light gets stronger, and water quality gets worse, frogs respond to that. If they get wiped out, we lose an important environmental signal,” Yacoub said.