New parasite discovered amid decline of California's unique Channel Island fox

 

California's Channel Islands are home to the Channel Island fox (Urocyon littoralis), one of the smallest and most cherished species of island fox in the United States. Although no longer on the Endangered Species List, they remain a species of special concern due to their ecological importance.

In the 1990s, the San Miguel Island fox nearly went extinct, dropping to just 15 individuals. A recovery program restored their numbers by 2010. However, from 2014 to 2018, the population fell to 30% of its peak right after a new acanthocephalan parasite, commonly known as thorny-headed worms, was identified on the island. This also occurred while a multi-year draught heated San Miguel Island, making it harder to identify the impact of the new parasite on San Miguel foxes.

To identify this parasite and determine the pathologic consequences of its infection on the health of foxes, a highly collaborative scientific effort, including a Florida Atlantic University researcher, used morphological and molecular methods to identify acanthocephalan parasites. They also used an extensive record of island fox necropsies and associated parasite collections to investigate the impact of the acanthocephalan parasite on the health of foxes at an individual and population level.

Results of the study, published in the International Journal for Parasitology, identify the parasite as Pachysentis canicola, a common acanthocephalan in multiple carnivore species in mainland North America. The parasite was detected in 69% of the necropsied foxes from San Miguel Island and was not found in any of the other five Channel Island fox subspecies.

Health issues linked to the acanthocephalan parasite, such as severe intestinal damage and inflammation, were seen in 47% of infected foxes. Other parasites did not significantly impact the health or survival rates of San Miguel Island foxes until the acanthocephalan arrived. After 2018, improved rainfall may have helped body condition recover, but it remained 27% lower than before the acanthocephalan outbreak, indicating that both environmental factors and parasites affect fox populations.

"We suspect that this parasite likely arrived on the island through infected arthropods such as insects inadvertently transported by humans," said Ale Aleuy, DVM, MPVM, Ph.D., senior author and an assistant professor in the FAU Department of Biological Sciences within the Charles E. Schmidt College of Science. "This discovery raises concerns about the impact of human activity on isolated ecosystems and underscores the importance of monitoring parasitic infections in vulnerable wildlife populations."

Researchers used detailed fox capture-recapture data from 4,269 captures of 846 foxes to investigate population health and demographic trends of foxes before and after the parasite was detected. They analyzed and monitored changes in body condition and weight from 2006 to 2022. Before the acanthocephalan arrived, the foxes had good health and low mortality despite other parasites.

"This parasite attaches to the intestinal wall of its host, which is particularly problematic for heavily infected foxes that exhibited more significant health issues such as emaciation, enteritis, and in some cases, death," said Aleuy. "After the parasite's arrival, foxes showed poorer body condition and lower weight, which worsened during drought conditions. This highlights the importance of understanding this parasite's life cycle and its impact on fox health, as well as preventing its spread to other Channel Islands."

Environmental stress may influence disease dynamics, and while foxes can survive with P. canicola in good conditions, they may need extra support during droughts.

"The acanthocephalan parasite did pose serious health challenges for the foxes, leading to issues like weight loss and intestinal complications. However, after the drought, we've seen a positive shift. While their condition is still not back to pre-parasite levels, the overall health of the foxes is stabilizing, and they are showing signs of improvement," said Aleuy. "This resilience gives us hope for their continued recovery."

The researchers suggest that it's also possible that P. canicola was present before 2012 but went undetected, potentially due to changes in fox diets increasing their exposure to intermediate hosts.

"Implementing appropriate management strategies is crucial to ensuring the health and longevity of this important species of fox," said Aleuy. "Controlling the invertebrates that spread the parasites might help, especially if they aren't native to the island."

The main goal is to prevent the parasite from spreading to other Channel Islands. Findings of this study highlight the importance of biosecurity in the Channel Islands National Park and more research on P. canicola and its impact on fox populations.

Journal Reference:

1. O. Alejandro Aleuy, Leslie W. Woods, Benjamin J. Padilla, Dennis Richardson, Juliann T. Schamel, Stacy Baker, Martín García-Varela, Charlotte Hammond, Sarah P. Lawson, Jasmine N. Childress, Jason Rohr, Kevin D. Lafferty. The invasive acanthocephalan parasite Pachysentis canicola is associated with a declining endemic island fox population on San Miguel Island. International Journal for Parasitology, 2024; DOI: 10.1016/j.ijpara.2024.09.003 

Courtesy:

Florida Atlantic University. "New parasite discovered amid decline of California's unique Channel Island fox." ScienceDaily. ScienceDaily, 23 October 2024. <www.sciencedaily.com/releases/2024/10/241023131048.htm>.

 

 

 

 

H5N1 virus isolated from infected dairy worker is 100% lethal in ferrets, but does not appear to be circulating in nature anymore

 

A strain of H5N1 avian influenza virus found in a Texas dairy worker who was infected this spring was able to spread among ferrets through the air, although inefficiently, and killed 100% of infected animals in studies University of Wisconsin-Madison researchers performed with the strain earlier this year.

The good news: the dairy worker experienced mild symptoms and fully recovered, and the H5N1 strain that infected the worker does not appear to have continued spreading in the wild.

Still, the findings highlight the risks posed by a virus that continues to spread among dairy cattle and occasionally to farm workers, and the study's lead scientist says he was surprised by the ease with which this particular strain was able to kill ferrets.

"This is one of the most pathogenic viruses I've ever seen in ferrets," says Yoshihiro Kawaoka, a UW-Madison professor of pathobiological sciences who spearheaded the work, described Oct. 28, 2024, in the journal Nature.

Ferrets are a common model for studying how influenza viruses that primarily affect birds are able to adapt to mammals, a topic that Kawaoka and his colleagues at UW-Madison's Influenza Research Institute investigate since such a jump could trigger an influenza pandemic.

Like other influenza viruses, H5N1 viruses mutate at a relatively rapid clip as they infect new hosts. Sometimes these mutations allow the viruses to more easily infect and spread among new species. That's how the current viruses, which have been infecting birds around the world in recent years, began to spread among mammals, most notably North American dairy cattle in 2024.

Kawaoka and his collaborators found that the H5N1 virus that infected the Texas dairy worker included a mutation that the team first identified in 2001 as important for causing severe disease. Luckily, Kawaoka says, the strain with that mutation seems to have died out.

"This isolate is unique among the H5N1 viruses circulating in cows," he says.

Kawaoka hypothesizes that H5N1 viruses took two paths when they made the jump from birds to cows, both facilitated by mutations that made the virus better adapted to mammals.

Kawaoka and his colleagues suggest that one path resulted in the more concerning mutation found in the Texas dairy worker, while the other led to a less dangerous mutation in the same protein.

"Both mutations give the virus the ability to adapt to mammals, but the good thing is the one containing this more pathogenic mutation has not been detected again," Kawaoka says. "So there are no extremely pathogenic H5N1 viruses currently circulating in cows. However, if a currently circulating cow H5N1 virus acquires that mutation, then that would be an issue."

Whether a virus with such a mutation would be dangerous for humans remains to be seen.

"The puzzling thing is why the human who got this virus did not have a severe infection," says Kawaoka, noting a few possibilities.

Perhaps exposure to seasonal influenza viruses provides some level of protection via antibodies, or maybe the route of infection is important; the Texas dairy worker's main symptom was conjunctivitis, suggesting the virus entered through the eye rather than the more typical respiratory route.

Alternatively, more robust surveillance of influenza cases among American dairy workers since the virus began spreading on farms might mean more cases -- including mild ones -- are being identified. Another possibility is this particular strain might simply be less severe in humans than mammals like ferrets.

"Those are all possibilities, but we don't know," says Kawaoka. "So, we're now trying to understand why this virus is so pathogenic in ferrets and what that could mean for human infections."

Journal Reference:

1. Chunyang Gu, Tadashi Maemura, Lizheng Guan, Amie J. Eisfeld, Asim Biswas, Maki Kiso, Ryuta Uraki, Mutsumi Ito, Sanja Trifkovic, Tong Wang, Lavanya Babujee, Robert Presler, Randall Dahn, Yasuo Suzuki, Peter J. Halfmann, Seiya Yamayoshi, Gabriele Neumann, Yoshihiro Kawaoka. A human isolate of bovine H5N1 is transmissible and lethal in animal models. Nature, 2024; DOI: 10.1038/s41586-024-08254-7 

Courtesy:

University of Wisconsin-Madison. "H5N1 virus isolated from infected dairy worker is 100% lethal in ferrets, but does not appear to be circulating in nature anymore." ScienceDaily. ScienceDaily, 28 October 2024. <www.sciencedaily.com/releases/2024/10/241028131451.htm>.

 

 

 

 

Age-old mystery solved: No more chicken or egg debate; scientists reveal who came first

 The age-old question of whether the chicken or the egg came first has puzzled minds for centuries. It’s a curious riddle that has sparked debate, humour, and even scientific investigation. To uncover the answer, we must delve into the fascinating history of eggs and the evolutionary journey of chickens, tracing back millions of years.

Eggs are widespread throughout the animal kingdom. Technically, an egg is a membrane-bound container where an embryo develops into an independent life. Eggs have been around since the evolution of the first amniotes, many millions of years ago. Early animals laid eggs in water, ensuring they didn’t dry out.

A crucial evolutionary step saw the emergence of amniotic eggs. These eggs developed three extra membranes: the chorion, amnion, and allantois. Together, they formed a complete life support system for embryos. This breakthrough enabled animals to lay eggs on land, offering embryos protection and nourishment without needing water.

According to the Australian Academy of Science, the first chicken emerged through genetic mutation. Two proto-chickens mated, passing on their DNA to create the first chicken. Genetic mutations occurred during this process, leading to the development of the very first chicken. This mutation was replicated in every cell as the chicken embryo grew.

Research suggests that amniotic eggs appeared roughly 340 million years ago, while chickens only evolved around 58,000 years ago. It’s reasonable to conclude that eggs predate chickens, as these eggs allowed various animal embryos to develop long before chickens existed.

However, chickens have a protein that plays a critical role in forming their eggs. This protein, called ovocleidin-17 (OC-17), is only found in chicken ovaries. Scientists argue that chickens must have come first because OC-17 is essential for forming eggshells, which are built within 24 hours.

The age-old debate

So, where does this leave the question? While eggs predate chickens, the specific formation of chicken eggs requires chickens for OC-17 production. Ultimately, chickens and their eggs are mutually dependent, making the answer far from simple.

Today’s eggs differ greatly from those produced by early birds. Industrialised farming methods focus on efficiency, with hens in controlled environments. Modern eggs meet strict safety standards, with options like free-range or organic eggs. In contrast, proto-eggs came from hens living freely, resulting in smaller production and different nutritional values.

Is eating chicken or eggs healthier?

Both chicken and eggs offer rich nutritional benefits. Chicken provides lean protein, vital vitamins like B3, and essential minerals, ideal for muscle growth and low-calorie diets. Eggs, meanwhile, deliver balanced protein, vitamins D and B12, and healthy fats. Eggs also contain antioxidants, supporting eye health. The choice between chicken and eggs ultimately depends on dietary preferences and needs.

 

Story by Neeshita Beura

Moneycontrol  

 

  

 

AI in healthcare: New research shows promise and limitations of physicians working with GPT-4 for decision making

 

Published in JAMA Network Open, a collaborative team of researchers from the University of Minnesota Medical School, Stanford University, Beth Israel Deaconess Medical Center and the University of Virginia studied how well doctors used GPT-4 -- an artificial intelligence (AI) large language model system -- for diagnosing patients.

The study was conducted with 50 U.S.-licensed physicians in family medicine, internal medicine and emergency medicine.

The research team found that the availability of GPT-4 to physicians as a diagnostic aid did not significantly improve clinical reasoning compared to conventional resources.

Other key findings include:

• GPT-4 alone demonstrated significantly better scores in diagnostic performance, surpassing the performance of clinicians using conventional diagnostic online resources and clinicians assisted by GPT-4.
• There was no significant enhancement in diagnostic performance with the addition of GPT-4 when assessing clinicians using GPT-4 against clinicians using conventional diagnostic resources.

"The field of AI is expanding rapidly and impacting our lives inside and outside of medicine. It is important that we study these tools and understand how we best use them to improve the care we provide as well as the experience of providing it," said Andrew Olson, MD, a professor at the U of M Medical School and hospitalist with M Health Fairview.

"This study suggests that there are opportunities for further improvement in physician-AI collaboration in clinical practice."

These results underline the complexity of integrating AI into clinical practice.

While GPT-4 alone showed promising results, the integration of GPT-4 as a diagnostic aid alongside clinicians did not significantly outperform the use of conventional diagnostic resources.

This suggests a nuanced potential for AI in healthcare, emphasizing the importance of further exploration into how AI can best support clinical practice.

Further, more studies are needed to understand how clinicians should be trained to use these tools.

The four collaborating institutions have launched a bi-coastal AI evaluation network -- known as ARiSE -- to further evaluate GenAI outputs in healthcare.

Funding for this research was provided by the Gordon and Betty Moore Foundation.

 

Journal Reference:

1. Ethan Goh, Robert Gallo, Jason Hom, Eric Strong, Yingjie Weng, Hannah Kerman, Joséphine A. Cool, Zahir Kanjee, Andrew S. Parsons, Neera Ahuja, Eric Horvitz, Daniel Yang, Arnold Milstein, Andrew P. J. Olson, Adam Rodman, Jonathan H. Chen. Large Language Model Influence on Diagnostic Reasoning. JAMA Network Open, 2024; 7 (10): e2440969 DOI: 10.1001/jamanetworkopen.2024.40969 

Courtesy:

University of Minnesota Medical School. "AI in healthcare: New research shows promise and limitations of physicians working with GPT-4 for decision making." ScienceDaily. ScienceDaily, 28 October 2024. <www.sciencedaily.com/releases/2024/10/241028164534.htm>.

 

 

Researchers develop 3D atlas of the developing mammalian brain

 

A 3D atlas of developing mice brains using advanced imaging and microscopy techniques has been created by a team of researchers at Penn State College of Medicine and collaborators from five different institutes. This new atlas provides a more dynamic, 360-degree picture of the whole mammalian brain as it develops during the embryonic and immediate post-natal stages and serves as a common reference and anatomical framework that will help researchers understand brain development and study neurodevelopmental disorders.

They published their work today (Oct 21) in Nature Communications.

"Maps are a fundamental infrastructure to build knowledge upon but we don't have a high-resolution 3D atlas of the developing brain," said Yongsoo Kim, associate professor of neural and behavioral sciences at Penn State College of Medicine and senior author on the paper. "We are generating high-resolution maps that we can use to understand how the brain grows under normal circumstances and what happens when a brain disorder emerges."

Geographical atlases are a collection of maps that provide a comprehensive view of the Earth's geography including boundaries between regions and countries, features like mountains and rivers, and thoroughfares like roads and highways. Importantly, they provide a common understanding that allows users pinpoint specific locations and understand the spatial relationship between regions.

Similarly, brain atlases are foundational for understanding the architecture of the brain. They help researchers visualize how the brain is organized spatially and understand brain structure, function, and how different regions and neurons are connected. Previously, scientists have been limited to 2D histology-based snapshots, which makes it challenging to interpret anatomical regions in three dimensions and any changes that may occur, Kim said.

In recent years, there has been tremendous progress in whole brain imaging techniques that let researchers look at the whole brain at high resolution and produce large-scale 3D datasets. To analyze this data, Kim explained, scientists have developed 3D reference atlases of the adult mouse brain, which is a model for the mammalian brain. The atlases provide a universal anatomical framework that allow researchers to overlay diverse datasets and conduct comparative analyses. However, there's no equivalent for the developing mouse brain, which undergoes rapid changes in shape and volume during the embryonic and post-natal stages.

"Without this 3D map of the developing brain, we cannot integrate data from emerging 3D studies into a standard spatial framework or analyze the data in a consistent manner," Kim said. In other words, the lack of a 3D map hinders the advancement of neuroscience research.

The research team created a multimodal 3D common coordinate framework of the mouse brain across seven developmental timepoints -- four points of time during the embryonic period and three periods during the immediate postnatal phase. Using MRI, they captured images of the brain's overall form and structure. They then employed light sheet fluorescence microscopy, an imaging technique that enables visualization of the whole brain at a single-cell resolution. These high-resolution images were then matched to the shape of the MRI templates of the brain to create the 3D map. The team pooled samples from both male and female mice.

To demonstrate how the atlas can be used to analyze different datasets and track how individual cell types emerge in the developing brain, the team focused on GABAergic neurons, which are nerve cells that play a key communication role in the brain. This cell type has been implicated in schizophrenia, autism and other neurological disorders.

While scientists have studied GABAergic neurons in the outermost region of the brain called the cortex, not much is known about how these cells arise in the whole brain during development, according to the researchers. Understanding how these clusters of cells develop under normal conditions may be key to assessing what happens when something goes awry.

To facilitate collaboration and further advancement in neuroscience research, the team created an interactive web-based version that is publicly available and free. The aim is to significantly lower technical barriers for researchers around the world to access this resource.

"This provides a roadmap that can integrate a lot of different data -- genomic, neuroimaging, microscopy and more -- into the same data infrastructure. It will drive the next evolution of brain research driven by machine learning and artificial intelligence," Kim said.

Journal Reference:

1. Fae N. Kronman, Josephine K. Liwang, Rebecca Betty, Daniel J. Vanselow, Yuan-Ting Wu, Nicholas J. Tustison, Ashwin Bhandiwad, Steffy B. Manjila, Jennifer A. Minteer, Donghui Shin, Choong Heon Lee, Rohan Patil, Jeffrey T. Duda, Jian Xue, Yingxi Lin, Keith C. Cheng, Luis Puelles, James C. Gee, Jiangyang Zhang, Lydia Ng, Yongsoo Kim. Developmental mouse brain common coordinate framework. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-53254-w 

Courtesy:

Penn State. "Researchers develop 3D atlas of the developing mammalian brain." ScienceDaily. ScienceDaily, 21 October 2024. <www.sciencedaily.com/releases/2024/10/241021123011.htm>.

 

 

 

 

Creating a simplified form of life

 

It is one of the most fundamental questions in science: how can lifeless molecules come together to form a living cell? Bert Poolman, Professor of Biochemistry at the University of Groningen, has been working on this problem for over twenty years. He aims to understand life by trying to reconstruct it; he is building simplified artificial versions of biological systems that can be used as components for a synthetic cell. Poolman recently published two papers in Nature Nanotechnology and Nature Communications. In the first paper, he describes a system for energy conversion and cross-feeding of products of this reaction between synthetic cells, while he describes a system for concentrating and converting nutrients in cells in the second paper.

Six Dutch research institutes are collaborating in the consortium BaSyc (Building a Synthetic Cell) to build the elements needed for a synthetic cell. Poolman's group has been working on energy conversion. The real-life equivalents he aims to replicate are mitochondria, the 'energy factories' of the cell. These use the molecule ADP to produce ATP, which is the standard 'fuel' that cells require to function. When ATP is converted back into ADP, the energy is released and used to drive other processes.

Artificial energy factories

'Instead of the hundreds of components of mitochondria, our system for energy conversion uses just five,' says Poolman. 'We set out to simplify it as much as possible.' This may sound odd, as evolution has done a great job of producing functional systems. 'However, evolution is a one-way street, it builds on existing components and this often makes the outcome very complex,' explains Poolman. An artificial replica, on the other hand, can be designed with a specific outcome in mind.

The five components were placed inside vesicles, tiny cell-like sacs, that can absorb ADP as well as the amino acid arginine from the surrounding fluid. The arginine is 'burned' (deaminated) and thus provides the energy to produce ATP, which is secreted from the vesicle. 'Of course, the simplification comes at a price: we can only use arginine as the energy source, while cells use all kinds of different molecules, such as amino acids, fats, and sugars.'

Next, the Poolman group designed a second vesicle that is able to absorb the secreted ATP and use it to drive an energy-consuming reaction. The energy is provided by turning ATP back into ADP, which is then secreted and can be absorbed by the first vesicle, closing the loop. Such a cycle of ATP production and use is the foundation of metabolism in every living cell and drives the 'machinery' for energy-consuming reactions such as growth, cell division, protein synthesis, DNA replication, and more.

An artificial pumping system

The second module that Poolman created was a bit different: a vesicle in which a chemical process causes the interior to build up a negative charge and, in doing so, form an electrical potential, similar to that of an electronic circuit. The electrical potential is used to couple charge movement to the accumulation of nutrients inside the vesicle, which is carried out by transporters. These proteins in the membrane of the vesicle work a bit like a water wheel: positively charged protons 'flow' through it from outside the vesicle to the negatively charged interior. This flow drives the transporter, which in this case imports a sugar molecule, lactose. Again, this is a very common process in living cells, requiring many components that Poolman and his team mimicked with just two components.

When he submitted a paper describing this system, a reviewer asked if he couldn't do something with the lactose that is being transported, as cells use nutrients like this to produce useful building blocks. Poolman took up the challenge and added three more enzymes to the system, which oxidized the sugar and enabled production of the coenzyme NADH. 'This helper molecule plays an essential role in the proper functioning of all cells,' explains Poolman. 'And by adding NADH production, we have shown that it is feasible to expand the system.'

But what about the synthetic cell?

Having a simplified synthetic equivalent of two key features of life is fascinating, but many more steps need to be integrated to form an autonomously growing and dividing synthetic cell. 'The next step we want to take is adding our metabolic energy producing systems to a synthetic cell division system created by colleagues,' says Poolman.

The BaSyc programme is entering its final years; funding for a new programme has recently been secured. A large consortium of Dutch groups, in which Poolman is one of the leading scientists, received 40 million euros to create life from non-living modules. This EVOLF project is set to run for another ten years and aims to find out how many more lifeless modules can come together and create living cells. 'Ultimately, this would give us a blueprint for life, something that is currently lacking in biology,' concludes Poolman. 'This may eventually have all kinds of applications, but will also help us to better understand what life is.'

Journal References:

1. Laura Heinen, Marco van den Noort, Martin S. King, Edmund R. S. Kunji, Bert Poolman. Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors. Nature Nanotechnology, 2024; DOI: 10.1038/s41565-024-01811-1
2. Miyer F. Patiño-Ruiz, Zaid Ramdhan Anshari, Bauke Gaastra, Dirk J. Slotboom, Bert Poolman. Chemiosmotic nutrient transport in synthetic cells powered by electrogenic antiport coupled to decarboxylation. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-52085-z 

Courtesy:

University of Groningen. "Creating a simplified form of life." ScienceDaily. ScienceDaily, 21 October 2024. <www.sciencedaily.com/releases/2024/10/241021123151.htm>.

 

 

 

Men and women process pain differently, study finds

 

In a new study evaluating meditation for chronic lower back pain, researchers at University of California San Diego School of Medicine have discovered that men and women utilize different biological systems to relieve pain. While men relieve pain by releasing endogenous opioids, the body's natural painkillers, women rely instead on other, non-opioid based pathways.

Synthetic opioid drugs, such as morphine and fentanyl, are the most powerful class of painkilling drugs available. Women are known to respond poorly to opioid therapies, which use synthetic opioid molecules to bind to the same receptors as naturally-occurring endogenous opioids. This aspect of opioid drugs helps explain why they are so powerful as painkillers, but also why they carry a significant risk of dependence and addiction.

"Dependence develops because people start taking more opioids when their original dosage stops working," said Fadel Zeidan, Ph.D., professor of anesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion. "Although speculative, our findings suggest that maybe one reason that females are more likely to become addicted to opioids is that they're biologically less responsive to them and need to take more to experience any pain relief."

The study combined data from two clinical trials involving a total of 98 participants, including both healthy individuals and those diagnosed with chronic lower back pain. Participants underwent a meditation training program, then practiced meditation while receiving either placebo or a high-dose of naloxone, a drug that stops both synthetic and endogenous opioids from working. At the same time, they experienced a very painful but harmless heat stimulus to the back of the leg. The researchers measured and compared how much pain relief was experienced from meditation when the opioid system was blocked versus when it was intact.

The study found:

• Blocking the opioid system with naloxone inhibited meditation-based pain relief in men, suggesting that men rely on endogenous opioids to reduce pain.
• Naloxone increased meditation-based pain relief in women, suggesting that women rely on non-opioid mechanisms to reduce pain.
• In both men and women, people with chronic pain experienced more pain relief from meditation than healthy participants.

"These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don't work nearly as well for women as they do for men," said Zeidan.

The researchers conclude that by tailoring pain treatment to an individual's sex, it may be possible to improve patient outcomes and reduce the reliance on and misuse of opioids.

"There are clear disparities in how pain is managed between men and women, but we haven't seen a clear biological difference in the use of their endogenous systems before now," said Zeidan. "This study provides the first clear evidence that sex-based differences in pain processing are real and need to be taken more seriously when developing and prescribing treatment for pain."

Co-authors on the study include Jon Dean, Mikaila Reyes, Lora Khatib, Gabriel Riegner, Nailea Gonzalez, Julia Birenbaum and Krishan Chakravarthy at UC San Diego, Valeria Oliva at Istituto Superiore di Sanità, Grace Posey at Tulane University School of Medicine, Jason Collier and Rebecca Wells at Wake Forest University School of Medicine, Burel Goodin at Washington University in St Louis and Roger Fillingim at University of Florida.

This study was funded, in part, by the National Center for Complementary and Integrative Health (grants R21-AT010352, R01-AT009693, R01AT011502) and the National Center for Advancing Translational Sciences (UL1TR001442).

Journal Reference:

1. Jon G Dean, Mikaila Reyes, Valeria Oliva, Lora Khatib, Gabriel Riegner, Nailea Gonzalez, Grace Posey, Jason Collier, Julia Birenbaum, Krishnan Chakravarthy, Rebecca E Wells, Burel Goodin, Roger Fillingim, Fadel Zeidan. Self-regulated analgesia in males but not females is mediated by endogenous opioids. PNAS Nexus, 2024; DOI: 10.1093/pnasnexus/pgae453 

Courtesy:

University of California - San Diego. "Men and women process pain differently, study finds." ScienceDaily. ScienceDaily, 16 October 2024. <www.sciencedaily.com/releases/2024/10/241016120023.htm>.

 

 

 

Viruses are teeming on your toothbrush, showerhead

 

Step aside tropical rainforests and coral reefs -- the latest hotspot to offer awe-inspiring biodiversity lies no further than your bathroom.

In a new Northwestern University-led study, microbiologists found that showerheads and toothbrushes are teeming with an extremely diverse collection of viruses -- most of which have never been seen before.

Although this might sound ominous, the good news is these viruses don't target people. They target bacteria.

The microorganisms collected in the study are bacteriophage, or "phage," a type of virus that infects and replicates inside of bacteria. Although researchers know little about them, phage recently have garnered attention for their potential use in treating antibiotic-resistant bacterial infections. And the previously unknown viruses lurking in our bathrooms could become a treasure trove of materials for exploring those applications.

The study will be published Wednesday (Oct. 9) in the journal Frontiers in Microbiomes.

"The number of viruses that we found is absolutely wild," said Northwestern's Erica M. Hartmann, who led the study. "We found many viruses that we know very little about and many others that we have never seen before. It's amazing how much untapped biodiversity is all around us. And you don't even have to go far to find it; it's right under our noses."

An indoor microbiologist, Hartmann is an associate professor of civil and environmental engineering at Northwestern's McCormick School of Engineering and a member of the Center for Synthetic Biology.

The return of 'Operation Pottymouth'

The new study is an offshoot of previous research, in which Hartmann and her colleagues at University of Colorado at Boulder characterized bacteria living on toothbrushes and showerheads. For the previous studies, the researchers asked people to submit used toothbrushes and swabs with samples collected from their showerheads.

Inspired by concerns that a flushing toilet might generate a cloud of aerosol particles, Hartmann affectionately called the toothbrush study, "Operation Pottymouth."

"This project started as a curiosity," Hartmann said. "We wanted to know what microbes are living in our homes. If you think about indoor environments, surfaces like tables and walls are really difficult for microbes to live on. Microbes prefer environments with water. And where is there water? Inside our showerheads and on our toothbrushes."

Diversity and opportunities

After characterizing bacteria, Hartmann then used DNA sequencing to examine the viruses living on those same samples. She was immediately blown away. Altogether, the samples comprised more than 600 different viruses -- and no two samples were alike.

"We saw basically no overlap in virus types between showerheads and toothbrushes," Hartmann said. "We also saw very little overlap between any two samples at all. Each showerhead and each toothbrush is like its own little island. It just underscores the incredible diversity of viruses out there."

While they found few patterns among all the samples, Hartmann and her team did notice more mycobacteriophage than other types of phage. Mycobacteriophage infect mycobacteria, a pathogenic species that causes diseases like leprosy, tuberculosis and chronic lung infections. Hartmann imagines that, someday, researchers could harness mycobacteriophage to treat these infections and others.

"We could envision taking these mycobacteriophage and using them as a way to clean pathogens out of your plumbing system," she said. "We want to look at all the functions these viruses might have and figure out how we can use them."

Most microbes 'will not make us sick'

But, in the meantime, Hartmann cautions people not to fret about the invisible wildlife living within our bathrooms. Instead of grabbing for bleach, people can soak their showerheads in vinegar to remove calcium buildup or simply wash them with plain soap and water. And people should regularly replace toothbrush heads, Hartmann says. Hartmann also is not a fan of antimicrobial toothbrushes, which she said can lead to antibiotic-resistant bugs.

"Microbes are everywhere, and the vast majority of them will not make us sick," she said. "The more you attack them with disinfectants, the more they are likely to develop resistance or become more difficult to treat. We should all just embrace them."

The study, "Phage communities in household-related biofilms correlate with bacterial hosts but do not associate with other environmental factors," was supported by Northwestern University.

Journal Reference:

1. Stefanie Huttelmaier, Weitao Shuai, Jack T. Sumner, Erica M. Hartmann. Phage communities in household-related biofilms correlate with bacterial hosts. Frontiers in Microbiomes, 2024; 3 DOI: 10.3389/frmbi.2024.1396560 

Courtesy:

Northwestern University. "Viruses are teeming on your toothbrush, showerhead." ScienceDaily. ScienceDaily, 9 October 2024. <www.sciencedaily.com/releases/2024/10/241009122630.htm>.

 

 

 

 

Large-scale atlas of how immune cells react to mutations during cancer immunotherapy

 

A Cleveland Clinic-led research collaboration between Timothy Chan, MD, PhD, Chair of Cleveland Clinic's Global Center for Immunotherapy, and Bristol Myers Squibb has published the most comprehensive overview to date of how the immune system reshapes tumor architecture in response to immune checkpoint therapy.

The eight-year study, published in Nature Medicine, outlines how cancer immunotherapy induces tumor recognition through neoantigens to reshape the tumor ecosystem. Neoantigens are small peptides produced when cancer cells mutate and are a primary marker for the immune system to recognize cancer cells as different from self.

"This study is unique in that we sampled tumors prior to therapy and then early after immunotherapy was initiated," explains Dr. Chan, who is also chair of Cleveland Clinic's Center for Immunotherapy & Precision Immuno-Oncology, program leader of Case Comprehensive Cancer Center's Immune Oncology Program and the Sheikha Fatima bint Mubarak Endowed Chair in Immunotherapy. "Our goal was to understand how patients' tumors are recognized and altered by their immune system in response to immunotherapy."

Our immune cells and cancer cells constantly interact and influence one another over the course of cancer. Immunotherapy treatments need to operate within that framework by boosting our immune cells to eliminate cancer. Scientists like Dr. Chan have begun to untangle the complex relationships between treatment, immunity and cancer in the past 15 years -- but human data is in short supply.

The CheckMate-153 trial was overseen by pharmaceutical company Bristol Myers Squibb and Dr. Chan's team was a central site for the trial's analysis. Within the primary trial, investigators included a biomarker sub-study to identify how neoantigens drive response to nivolumab by sampling patients' tumors pre-therapy and 3 weeks post-therapy. From these tumor samples, sequencing was used to identify mutations that create neoantigens.

Neoantigens are thought to be the primary way that the immune system recognizes tumors, but neoantigen prediction tools lack accuracy due to lack existing data in this space. To overcome this issue the team developed the largest neoantigen screen to date, where they validated their predictions and monitored the dynamic response to neoantigens with longitudinal blood draws.

Within three weeks of treatment, people who went on to respond well to nivolumab had a sharp decline in clonal neoantigens. Meanwhile, individuals whose cancer did not go into remission still mounted an immunologic response but to smaller sub-clonal populations. This is important because many believed that non-responders were unable to activate and recognize tumor, but here they show it may be that the immune system is mounting a response to neoantigens but that this is insufficient to destroy all tumor clones.

Current neoantigen prediction tools rely heavily on HLA-binding neoantigens, but they are missing the T cell recognition aspect of immunogenicity, says Cleveland Clinic's co-first author Tyler Alban, PhD, Project Staff in the Chan Lab. Dr. Alban, data scientist Prerana Parthasarathy, and others on the team developed a machine-learning program that uses the new screening data to better predict immunogenic neoantigens. In the process, the program identified novel features harbored by these cancer-derived neoantigens.

"We observed a whole ecosystem of immune cells at work, with each T cell recognizing a different neoantigen altering the clonal makeup of the tumor," Dr. Alban says. "Our data let us generate new insights into neoantigens and resistance to immunotherapy."

By cataloguing changes to neoantigens during treatment, Dr. Alban's analyses challenged the prevailing theory in immunotherapy: that a tumor only needs one lucky mutation to develop features our immune systems recognize as a threat. The results show that many different T cells recognizing many different cancer-causing features are needed to respond well to treatment.

Roadmaps generated by these types of observational studies will be critical in navigating future immuno-oncology research, Dr. Chan says.

"Learning why our immune systems respond to some cancerous mutations but not others are like the holy grail for immunotherapy researchers," he explains. "Our findings are one of the closest things we have to figuring these things out."

The group is also using their dataset in collaboration with IBM in the Cleveland Clinic -- IBM Discovery Accelerator to more advanced AI models that predict new molecules for cancer treatments and cancer vaccine development.

Journal Reference:

1. Tyler J. Alban, Nadeem Riaz, Prerana Parthasarathy, Vladimir Makarov, Sviatoslav Kendall, Seong-Keun Yoo, Rachna Shah, Nils Weinhold, Raghvendra Srivastava, Xiaoxiao Ma, Chirag Krishna, Juk Yee Mok, Wim J. E. van Esch, Edward Garon, Wallace Akerley, Benjamin Creelan, Nivedita Aanur, Diego Chowell, William J. Geese, Naiyer A. Rizvi, Timothy A. Chan. Neoantigen immunogenicity landscapes and evolution of tumor ecosystems during immunotherapy with nivolumab. Nature Medicine, 2024; DOI: 10.1038/s41591-024-03240-y 

Courtesy:

Cleveland Clinic. "Large-scale atlas of how immune cells react to mutations during cancer immunotherapy." ScienceDaily. ScienceDaily, 1 October 2024. <www.sciencedaily.com/releases/2024/10/241001152944.htm>.

 

 

 

 

New paradigm of drug discovery with world's first atomic editing?

In pioneering drug development, the new technology that enables the easy and rapid editing of key atoms responsible for drug efficacy has been regarded as a fundamental and "dream" technology, revolutionizing the process of discovering potential drug candidates. KAIST researchers have become the first in the world to successfully develop single-atom editing technology that maximizes drug efficacy.

On October 8th, KAIST (represented by President Kwang-Hyung Lee) announced that Professor Yoonsu Park's research team from the Department of Chemistry successfully developed technology that enables the easy editing and correction of oxygen atoms in furan compounds into nitrogen atoms, directly converting them into pyrrole frameworks, which are widely used in pharmaceuticals.

This research was published in the scientific journal Science on October 3rd under the title "Photocatalytic Furan-to-Pyrrole Conversion."

Many drugs have complex chemical structures, but their efficacy is often determined by a single critical atom. Atoms like oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, particularly against viruses.

This phenomenon, where the introduction of specific atoms into a drug molecule dramatically affects its efficacy, is known as the "Single Atom Effect." In leading-edge drug development, discovering atoms that maximize drug efficacy is key.

However, evaluating the Single Atom Effect has traditionally required multi-step, costly synthesis processes, as it has been difficult to selectively edit single atoms within stable ring structures containing oxygen or nitrogen.

Professor Park's team overcame this challenge by introducing a photocatalyst that uses light energy. They developed a photocatalyst that acts as a "molecular scissor," freely cutting and attaching five-membered rings, enabling single-atom editing at room temperature and atmospheric pressure -- a world first.

The team discovered a new reaction mechanism in which the excited molecular scissor removes oxygen from furan via single-electron oxidation and then sequentially adds a nitrogen atom.

Donghyeon Kim and Jaehyun You, the study's first authors and candidates in KAIST's integrated master's and doctoral program in the Department of Chemistry, explained that this technique offers high versatility by utilizing light energy to replace harsh conditions. They further noted that the technology enables selective editing, even when applied to complex natural products or pharmaceuticals. Professor Yoonsu Park, who led the research, remarked, "This breakthrough, which allows for the selective editing of five-membered organic ring structures, will open new doors for building libraries of drug candidates, a key challenge in pharmaceuticals. I hope this foundational technology will be used to revolutionize the drug development process."

The significance of this research was highlighted in the Perspective section of Science, a feature where a peer scientist of prominence outside of the project group provides commentary on an impactful research.

This research was supported by the National Research Foundation of Korea's Creative Research Program, the Cross-Generation Collaborative Lab Project at KAIST, and the POSCO Science Fellowship of the POSCO TJ Park Foundation.

Journal Reference:

1. Donghyeon Kim, Jaehyun You, Da Hye Lee, Hojin Hong, Dongwook Kim, Yoonsu Park. Photocatalytic furan-to-pyrrole conversion. Science, 2024; 386 (6717): 99 DOI: 10.1126/science.adq6245 

Courtesy:

The Korea Advanced Institute of Science and Technology (KAIST). "New paradigm of drug discovery with world's first atomic editing?." ScienceDaily. ScienceDaily, 11 October 2024. <www.sciencedaily.com/releases/2024/10/241011141546.htm>.

 

 

 

 

Kerala is detecting ‘brain eating amoeba’ cases like never before – and saving its patients too

 

An alert medical fraternity and public, aggressive investigation, and a standard operating procedure – these are the major reasons why Kerala has been able to bring down mortality rate in the rare primary amoebic meningoencephalitis (PAM), commonly called the “brain eating amoeba”, from the 97 percent globally to 26 percent in Kerala.

Amoebic meningoencephalitis is caused by Naegleria fowleri, a free-living amoeba found in warm, fresh water and soil, and infects people when it enters the body through the nose.

According to the data submitted by Kerala health minister Veena George in the state Assembly early this week, of the 29 PAM cases that Kerala has reported so far in 2024, only five have died. State health department pegs the mortality rate for the disease at 26 percent – considerably lower than the 97 percent globally.

This is despite the jump in the number of cases in Kerala – according to state government data, cases have gone from just eight between 2016 and 2023 to 29 this year. Significantly, six districts had reported the PAM cases during the period, with Thiruvananthapuram having recorded the bulk of it at 15.

Of the 29 cases seen so far this year, 24 have survived. In contrast, according to the US Centres for Disease Control and Prevention, between 1962 and 2023, there were 164 reported cases of PAM in the United States, and only four survived.

The first case of PAM in India was reported in 1971, and the country has seen just around two dozen cases since then until last year. The first case in Kerala was reported in 2016.

All reported cases in India had led to the patient’s death – that is, until July this year, when 14-year-old Afanan Jasim from Thikkodi in Kerala’s Kozhikode district became the first Indian to survive the disease. He was only the 11th PAM survivor in the world.

The spike in cases this year is attributed to increased testing for acute encephalitis syndrome (AES) – a condition that can be caused by various diseases including amoebic meningoencephalitis – as well as other factors such as climate change and environmental pollution.

In July, Kerala issued a special treatment protocol and a standard operating procedure for the management of amoebic meningoencephalitis cases – the first state in India to do so.

According to Dr R Aravind, head of department of infectious diseases at the Government Medical College Thiruvananthapuram, the guidelines issued by the state health department on prevention, diagnosis and treatment of amoebic meningoencephalitis were a game changer for the state’s battle against the disease.

“The guidelines had stated a clear protocol to be followed, in which case one should suspect amoebic meningoencephalitis and what should be the medicine. Use of miltefosine was another major factor in the treatment, leading to reducing mortality. Until last year when we used a combination of four drugs (Amphotericin B, Rifampicin, Fluconazole and Azithromycin) and nobody survived. But the cocktail of these five drugs, including miltefosine, was another milestone in our fight against the fatal disease. As miltefosine was not easily available in India, the state health department took a very proactive stand and procured it from abroad.’

More cases are being detected because of aggressive search for amoebic meningoencephalitis cases.

Dr T S Anish, who is a member of the state medical board for PAM, said the increase in awareness of the disease among the doctors and the public helped detect more cases. According to him, the high instances of diagnosis of AES in the state was another major reason why doctors in Kerala were able to detect amoebic meningoencephalitis and Nipah cases more than anywhere else in the country.

“A few back-to-back deaths have also increased this awareness. Doctors have been sensitised. Now, if a patient is admitted with symptoms of encephalitis, they are ready to share the history of swimming in ponds or lakes, if any. This helps early diagnosis, which is vital for treatment of PAM. Thus, we have saved lives (in cases where PAM) would have gone undetected,” said Dr Anish, a professor of community medicine at the Government Medical College Manjeri, Malappuram.

The tropical climate of the state increases the chances of infection, he said.

“Due to global warming, the presence of naegleria fowleri has increased in ponds… We have other amoebae, too, which have become ubiquitous. But finding them is very tricky and there is a knowledge gap” he said.

Despite the fatality rate being pegged at 26 percent, sources in the health department believe the actual rate would be much lower.

According to the health department source, Kerala has reported two types of amoebae that cause brain infections. “We have cases reported from Kerala due to amoebas naegleria, which has a mortality rate of 97 percent, and acanthamoeba, which has mortality 60-90 percent. Hence, the state’s fatality rate was pegged at 26 percent,” the source said.

This finding of meningoencephalitis due to acanthamoeba, according to Dr Aravind, helped Kerala health department to go a step further in detecting the infection.

“When we were doing molecular diagnosis of meningoencephalitis, we learned that apart from naegleria fowleri, another genus acanthamoeba is also causing the infection. The notion that water exposure leads to amoebic meningoencephalitis is applicable only to cases caused by naegleria fowleri. Water exposure is not essentially applicable to meningoencephalitis caused by other amoeba including acanthamoeba, which has an incubation period from days to months,” he said.

Kerala had PAM cases without a history of water exposure, he said.

“The research papers published by School of Tropical Medicine, Kolkata, last year, had mentioned meningoencephalitis cases without water contact. Their experience also made us go for aggressive testing of meningoencephalitis cases without history of water contact. That helped us pick up more cases, particularly in Thiruvananthapuram,” he said.

Meanwhile, the state government has commissioned a study to analyse the organic and inorganic factors that contribute to increase in the density of amoeba in water bodies. The study will be conducted by Kerala University’s Department of Environmental Sciences and the State Pollution Control Board.

According to the University Prof Salom Gnana Thanka, who is part of the expert team, the density of amoeba will be high in contaminated water. “Besides, increase in temperature is also another contributing factor. We have literature from abroad in this regard but we have to study this situation in Indian conditions. We will be collecting samples of water mainly from areas where PAM cases were reported,” she said.

 https://indianexpress.com/article/india/kerala-is-detecting-brain-eating-amoeba-cases-like-never-before-and-saving-its-patients-too-9617472/

Courtesy: © The Indian Express Pvt Ltd