Publisher Health

Researchers have shown for the first time in mice that heart problems associated with the flu are not caused by raging inflammation in the lungs, as has long been predicted.
Instead, the Ohio State University study revealed, the electrical malfunctions and heart scarring seen in some of the sickest flu patients are caused by direct influenza infection of cardiac cells.
The research team had seen flu viral particles in cardiac cells of infected mice in previous work, but couldn’t say for sure their presence in the heart was driving cardiac damage. When researchers infected mice with a genetically altered flu virus that wasn’t able to replicate in heart cells, the mice developed classic inflammatory flu symptoms — but no cardiac complications.
“We showed that even when you have a very severe infection in the lungs, if you’re using that virus that can’t replicate in the heart, you don’t get those cardiac complications,” said lead author Jacob Yount, associate professor of microbial infection and immunity in Ohio State’s College of Medicine.
“It proves it’s direct infection of the heart that’s driving these complications. Now we need to figure out what direct infection does: Is it killing heart cells? Does it have long-term ramifications? Do repeated infections have heart complications that build up over time? There are a lot of questions now for us to answer.”
The study is published today (May 11, 2022) in the journal Science Advances.

Neurodegenerative diseases damage and destroy neurons, ravaging both mental and physical health. Parkinson’s disease, which affects over 10 million people worldwide, is no exception. The most obvious symptoms of Parkinson’s disease arise after the illness damages a specific class of neuron located in the midbrain. The effect is to rob the brain of dopamine — a key neurotransmitter produced by the affected neurons.
In new research, Jeffrey Kordower and his colleagues describe a process for converting non-neuronal cells into functioning neurons able to take up residence in the brain, send out their fibrous branches across neural tissue, form synapses, dispense dopamine and restore capacities undermined by Parkinson’s destruction of dopaminergic cells.
The current proof-of-concept study reveals that one group of experimentally engineered cells performs optimally in terms of survival, growth, neural connectivity, and dopamine production, when implanted in the brains of rats. The study demonstrates that the result of such neural grafts is to effectively reverse motor symptoms due to Parkinson’s disease.
Stem cell replacement therapy represents a radical new strategy for the treatment of Parkinson’s and other neurodegenerative diseases. The futuristic approach will soon be put to the test in the first of its kind clinical trial, in a specific population of Parkinson’s disease sufferers, bearing a mutation in the gene parkin. The trial will be conducted at various locations, including the Barrow Neurological Institute in Phoenix, with Kordower as principal investigator.
The work is supported through a grant from the Michael J. Fox Foundation.
“We cannot be more excited by the opportunity to help individuals who suffer from this genetic form of Parkinson’s disease, but the lessons learned from this trial will also directly impact patients who suffer from sporadic, or non-genetic forms of this disease,” Kordower says.

For patients suffering from multiple sclerosis (MS), becoming a mother is fraught with difficult questions: is it acceptable to continue disease modifying treatment during pregnancy and breastfeeding to keep the disease at bay, or does this put the child at risk? A study conducted by the neurology department of Ruhr-Universität Bochum (RUB) at St. Josef Hospital on the drug glatiramer acetate can relieve mothers of this concern during the breastfeeding period. A comparative study between children whose mothers had taken the drug while breastfeeding and those who hadn’t revealed no significant differences in several infant health outcomes during the first 18 months of life.
Consequently, the drug’s label, which is marketed under the name Copaxone, has been updated. The researchers published their findings in Multiple Sclerosis Journal from 1 April 2022.
Reducing frequency of relapses
Multiple sclerosis affects women two to three times more often than men, and most patients are diagnosed in childbearing age. The majority of patients suffer from relapsing MS, in which episodes with more severe symptoms alternate with episodes without symptoms. But, as the disease progresses, the nervous system is damaged by these recurrent episodes. This often results in permanent disability. Disease modifying therapies can slow down the accumulation of permanent damage to the central nervous system by reducing the frequency of episodes and prolonging the periods of stability between them. Glatiramer acetate is one of these drugs.
No negative effects recorded
“In this study, we compared the development of 120 children in total, whose mothers suffer from MS; 50 per cent of the mothers in this cohort had been treated with glatiramer acetate during lactation,” explains Dr. Andrea Ciplea from Professor Kerstin Hellwig’s research group at the RUB clinic. During the first 18 months of life the researchers monitored infant body measurements, developmental delays as well as antibiotic treatments and inpatient hospital stays. “We didn’t observe negative effects attributable to the administration of the MS drug,” points out Ciplea. As a result, Copaxone’s label has been updated and treatment with glatiramer acetate during breastfeeding period is now approved.
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen. Note: Content may be edited for style and length.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their accompanying protein, CRISPR-associated protein 9 (Cas9), made international headlines a few years ago as a game-changing genome editing system. Consisting of Cas9 and strand of genetic material known as a single-guide RNA (sgRNA), the system can target specific regions of DNA and function as ‘molecular scissors’ to make precise edits. The direct delivery of Cas9-sgRNA complexes, i.e. Cas9 ribonucleoproteins (RNPs) into the nucleus of the cell is considered the safest and most efficient way to achieve genome editing. However, the Cas9 RNP has poor cellular permeability, and thus requires a carrier molecule to transport it past the first hurdle of the cell membrane before it can get to the cell nucleus. These carriers need to bind with Cas9 RNP, carry it into the cell, prevent its degradation by intracellular organelles called ‘endosomes,’ and finally release it without causing any changes to its structure.
In a recent paper published in June 2022 in Volume 27 of Applied Materials Today, a research team from Kumamoto University has developed a transformable polyrotaxane (PRX) carrier that can facilitate genome editing using Cas9RNP with high efficiency and usability. “While there have been some PRX-based drug carriers for nucleic acids and proteins reported before, this is the first report on PRX-based Cas9 RNP carrier. Moreover, our findings describe how to precisely control intracellular dynamics across multiple steps. This will prove invaluable for future research in this direction,” says Professor Keiichi Motoyama, a corresponding author of the paper.
For their novel carrier, the research team focused on PRX with amine groups, i.e. amino-PRX, and went through multiple rounds of development and optimization before achieving their final product. For example, the first generation (1G) of their carrier molecules, exploited the autonomous transforming properties of amino-PRX to efficiently complex it with Cas9 RNP and enable its delivery past the cell membrane. The second generation (2G) worked towards endosome-escape. This was achieved via the transformation of the amino-groups in amino-PRX into highly cationic (positively charged) particles within the endosome, which resulted in the rupturing of the endosome and the escape of Cas9 RNP-amino-PRX. The next few generations addressed problems relating to the release of Cas9 once the complex had escaped the endosome. Finally, they developed the fifth generation (5G) multi-step transformable amino-PRX carrier that could precisely and efficiently deliver Cas9 RNP into the cell nucleus. The research team further performed in vitro and in vivo experiments to confirm the cytotoxicity of the system, as well as its genome editing efficiency. “Our delivery system has a low cytotoxicity and its genome editing activity is equal to the current most efficient system on the market,” reveals Associate Professor Taishi Higashi of Kumamoto University, who is the other corresponding author of the study. “Moreover, our multiple attempts at optimizing the delivery system across generations offers important information on the types and positions of various biodegradable groups and amino groups that can be used in such a system to further customize and adapt their properties.”
The autonomous action, multi-step transformable properties, and low cytotoxicity of the 5G amino-PRX carrier make it an enormously promising candidate for the safe and efficient delivery of Cas9 RNP. These findings could furthermore be applied for the delivery of a wide range of molecules, such as enzymes, antibodies, and small interfering RNA (siRNA), thereby making this novel carrier a significant achievement in the field of drug and vaccine development.
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A team of Clemson University scientists is making inroads in understanding the relationship between certain enzymes that are normally produced in the body and their role in regulating obesity and controlling liver diseases.
According to Centers for Disease Control and Prevention (CDC) data collected in 2017-18, more than 42% of U.S. adults and 19% of U.S. youths are obese.
Three Clemson researchers and colleagues from the Emory University School of Medicine studied male mice that lacked the Cyp2b enzyme and how the lack of the enzyme affected the mice’s metabolism.
William Baldwin, a professor and graduate program coordinator in Clemson’s Department of Biological Sciences, said the research was triggered in part by a simple observation: male mice that lacked the Cyp2b enzyme were putting on weight. The same effect was not noticed in female Cyp2b-null mice.
“We noticed that our Cyp2b-null mice were heavier,” said Baldwin, a professor in the department of biological sciences. “They are more prone to obesity — at least, diet-induced obesity — especially in males than are wild-type mice, and we were trying to find out why that is.”
While the observation that tipped off the researchers was pretty straightforward, it turned out that understanding the interactions behind the weight gain would be much more complex.

Though an essential gateway to the liver, NTCP had not been well described until now. Na+-taurocholate co-transporting polypeptide (NTCP) is a protein located exclusively in the membrane of liver cells that enables recycling of bile acid molecules. It is also the cellular receptor of human hepatitis B and D viruses (HBV/HDV). A better understanding of NTCP could enable the development of treatments specifically designed for the liver, and to fight HBV and HDV infection.
NTCP is a difficult protein to study. It weighs only 38 kilodaltons (kDa)1, whereas cryo-electron microscopy, the technology used to study this type of molecule, only works for molecules weighing more than 50 kDA. The challenge was therefore to “enlarge” and stabilise it.
To do this, teams from French and Belgian laboratories2 developed and tested a collection of antibody fragments targeting NTCP. The 3D structures of the resulting complexes were determined using cryo-electron microscopy, and different antibody fragments stabilised and revealed several forms of NTCP.
The research team was able to describe two essential NTCP conformations: one in which the protein opens a large membrane pore to bile salts, to which HBV and HDV can bind, and a second, ‘closed’ conformation, that prevents recognition by the viruses.
The first, ‘open’ conformation is very surprising, as no other known molecular transporter forms such a ‘wide open’ pore. In turn, the second conformation could help finding antiviral molecules that prevent HBV and HDV infection. The research team intends to continue its work to fully elucidate the functioning of NTCP.
Footnotes
1- One dalton is one-twelfth the mass of a carbon-12 atom (the mass of a hydrogen atom, approximately).
2- The study was conducted by teams at the MPF Laboratory (Microbiologie fondamentale et pathogénicité) (CNRS/University of Bordeaux), the Membrane Protein Mechanisms Unit at the Institut Pasteur, and the VIB-VUB Center for Structural Biology. This study was supported by the ANRS Emerging Infectious Diseases Program, among others.
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More than 40 million Americans take statins, the most common type of prescription drug. While statins have been shown to effectively lower cholesterol levels and reduce the risks of stroke and heart attack, they do not work the same for everyone, and side effects of statin use include an increased risk of developing type 2 diabetes.
Researchers from Institute for Systems Biology have shown that different patient responses to statins can be explained by the variation in the human microbiome. The findings were published today in the journal Med, and offer promising avenues for optimizing precision statin treatments for individual patients.
The research team found that the composition and diversity of the gut microbiome is predictive of the efficacy of statins and the magnitude of negative side effects.
“Specifically, we found that a Bacteroides enriched microbiome with lower levels of diversity was associated with the strongest LDL-lowering response to statins, but also coincided with the greatest disruption to blood glucose levels,” said Dr. Tomasz Wilmanski, lead author of the study.
The team also found that individuals with a Ruminococcaceae enriched microbiome were protected from the negative side effects of statins on insulin resistance while also showing a clear LDL-lowering response.
Wimanski and his colleagues built statistical models with microbiome, metabolome, human genome, and clinical records from an American cohort of more than 1,800 people and made their initial discoveries about variable statin effects on both cholesterol and blood glucose markers. Next, they validated their results in an independent European cohort of nearly 1,000 people.
The unique combination of microbiome and genomic information in this study provides exciting new insights into potential approaches to precision drug treatments.
The genetic fingerprint of a patient, which includes known genetic markers of statin treatment response, has already been leveraged in the clinic to guide personalized statin treatment regimes. In this study, the authors found that the variability in statin responses explained by the microbiome were completely independent of the variability captured by the genome. “It’s a completely different axis of variability, so we’re able to build models including both genetics and the gut microbiome to improve our statin response predictions,” Wilmanski said. “The genome and the microbiome, together, appear to provide a more comprehensive and complementary picture of personalized drug responses.”
A logical follow-up to this work is a clinical trial. “It would be great to take this knowledge about the genome and the microbiome and predict personalized dosing regimens for a cohort of patients, and then follow these patients forward in time, tracking their metabolic health and their LDL cholesterol levels, to show that this population of patients undergoing a precision intervention do better than a control group of patients who are getting what is normally prescribed,” said ISB Assistant Professor Dr. Sean Gibbons, a corresponding author on the paper.
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Some rare cases of higher genetic mutation rates in children, known as hypermutation, could be linked to the father receiving certain chemotherapy treatments, new research has found.
Scientists from the Wellcome Sanger Institute and their collaborators analysed over 20,000 families’ genetic information and identified 12 children with between two to seven times more mutations than the general population. The team linked the majority of these to increased mutations in the sperm of the biological father.
The research, published today (11 May 2022) in Nature, shows that just under half of these fathers had been treated with certain types of chemotherapy earlier in life, which could be linked to the increased number of mutations in their sperm cells.
While these cases of hypermutation in children are rare, and in the vast majority of children will not lead to genetic disorders, hypermutation will increase the risk of a child having a rare genetic disorder. It is important to investigate this further due to the implications it has for patients who receive chemotherapy and want to have children in the future.
If further research confirms an impact of chemotherapy, patients could be offered the opportunity to freeze their sperm before treatment.
Genomes are copied with a very low error rate when they are passed from one generation to the next. Nevertheless, as the human genome contains three billion letters, random mutations in the sperm and the egg are inevitable and pass from the parent to the child. This means that typically every child has around 60 to 70 new mutations that their biological parents don’t have. These mutations are responsible for genetic variation along with many genetic diseases. Around 75 per cent of these random mutations come from the father1.

Scientists have revived light-sensing neuron cells in organ donor eyes and restored communication between them as part of a series of discoveries that stand to transform brain and vision research.
Billions of neurons in the central nervous system transmit sensory information as electrical signals; in the eye, specialized neurons known as photoreceptors sense light.
Publishing in Nature, a team of researchers from the John A. Moran Eye Center at the University of Utah and Scripps Research collaborators describe how they used the retina as a model of the central nervous system to investigate how neurons die — and new methods to revive them.
“We were able to wake up photoreceptor cells in the human macula, which is the part of the retina responsible for our central vision and our ability to see fine detail and color,” explains Moran Eye Center scientist Fatima Abbas, PhD, lead author of the published study. “In eyes obtained up to five hours after an organ donor’s death, these cells responded to bright light, colored lights, and even very dim flashes of light.”
While initial experiments revived the photoreceptors, the cells appeared to have lost their ability to communicate with other cells in the retina. The team identified oxygen deprivation as the critical factor leading to this loss of communication.
To overcome the challenge, Scripps Research Associate Professor Anne Hanneken, MD, procured organ donor eyes in under 20 minutes from the time of death, while Moran Eye Center scientist Frans Vinberg, PhD, designed a special transportation unit to restore oxygenation and other nutrients to the organ donor eyes.

A receptor that was first identified as necessary for insulin action, that also is located on the neural stem cells found deep in the brains of mice, is pivotal for brain stem cell longevity, according to a Rutgers study, a finding that has important implications for brain health and future therapies for brain disorders.
The study, appearing in the journal Stem Cell Reports, pinpoints a specific protein known as the insulin receptor (INSR), which is abundant on the neural stem cells that reside in the brain’s subventricular zone. During development, neural stem cells give rise to the entire nervous system, and they persist into adulthood. Over the lifespan these neural stem cells produce new neurons and non-neuronal cells that maintain the infrastructure and functioning of the brain.
Separately, the scientists made another finding when examining brain tumors: INSR plays a crucial role in sustaining and maintaining a population of specialized brain cancer cells known as glioblastoma (GBM) stem cells. When they inactivated the INSR in the GBM stem cells they inhibited the growth of those primitive tumor forming cells.
“It’s important to understand the molecular mechanisms that are critical for the growth and sustenance of the brain’s stem cells under normal and abnormal growth states,” said study author Steven Levison, a professor of neuroscience in the Department of Pharmacology, Physiology and Neuroscience and director of the Laboratory for Regenerative Neurobiology at Rutgers New Jersey Medical School. “Comprehending the signals that regulate these primitive cells could one day lead to new therapeutics for brain disorders.”
Many neurodegenerative disorders, such as multiple sclerosis, Parkinson disease and Alzheimer’s disease, are connected with the destruction of brain cells, said co-author Teresa Wood, a Distinguished Professor and Rena Warshow Endowed Chair in Multiple Sclerosis in the Department of Pharmacology, Physiology and Neuroscience at Rutgers New Jersey Medical School.
“If we could influence how brain stem cells function then we can use this knowledge to replace diseased or dead brain cells with living ones, which would advance the treatment of neurological diseases and brain injuries,” said Wood, who also teaches and conducts research at the Cancer Institute of New Jersey.
Cell receptors such as INSR are protein molecules that reside on the surfaces of cells. Substances, either natural or human-made, that open the “lock” of a receptor can spur a cell to divide, differentiate or die. By identifying which receptors perform these functions on specific cell types, and by understanding their structures and functions, scientists can design substances that act as keys to receptors, to turn them “on” or “off.”
Previous studies by this research team had shown that a certain “key,” the signaling protein known as the insulin-like growth factor-II (IGF-II), was necessary to maintain the neural stem cells in the two places of the adult brain that harbor these primitive cells. In the current experiment, scientists were looking to identify the receptor. To do so, they used genetic tools that allowed them to both delete the INSR and introduce a fluorescent protein so they could track the neural stem cells and the cells they generate. They found that the numbers of neural stem cells in the subventricular zone in the brains of mice lacking the INSR collapsed.
Adult neurogenesis — the idea that new cells are produced in the adult brain — has been a burgeoning field of scientific inquiry since the late 1990s, when researchers confirmed what had only been a theory in lab studies of human, primate and bird brains. Neural stem cells in the adult are stem cells that can self-renew and produce new neurons and the supporting cells of the brain, oligodendrocytes and astrocytes.
“Given the widespread interest in stem cells as well as interest in whether alterations to adult stem cells might contribute to cancer, our research findings should be of interest,” Levison said.
Other Rutgers authors included Shravanthi Chidambaram, Fernando J. Velloso, Deborah E. Rothbard, Kaivalya Deshpande and Yvelande Cajuste of the Department of Pharmacology, Physiology and Neuroscience at Rutgers New Jersey Medical School. Other participating investigators were at the University of Minnesota, the Albert Einstein College of Medicine and Brown University.
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Materials provided by Rutgers University. Original written by Kitta MacPherson. Note: Content may be edited for style and length.