Glass Frogs Living Near Roaring Waterfalls Wave Hello to Attract Mates (Biology)

Most frogs emit a characteristic croak to attract the attention of a potential mate. But a few frog species that call near loud streams — where the noise may obscure those crucial love songs — add to their calls by visually showing off with the flap of a hand, a wave of a foot or a bob of the head. Frogs who “dance” near rushing streams have been documented in the rainforests of India, Borneo, Brazil and, now, Ecuador.

A UC Berkeley conservation ecologist has discovered that an elusive glass frog species (Sachatamia orejuela) uses both high-pitched calls and visual signaling — in the form of hand-waving, foot-waving and head-bobbing — to communicate near loud waterfalls. (Photo courtesy Rebecca Brunner)

Conservation ecologist Rebecca Brunner, a Ph.D. candidate at the University of California, Berkeley, has discovered that the glass frog Sachatamia orejuela can be added to the list of species that make use of visual cues in response to their acoustic environments. This is the first time a member of the glass frog family (Centrolenidae) has been observed using visual communication in this manner.

“A handful of other frog species around the world use visual signaling, in addition to high-pitched calls, to communicate in really loud environments,” Brunner said. “What’s interesting is that these species are not closely related to each other, which means that these behaviors likely evolved independently, but in response to similar environments — a concept called convergent evolution.”

Video: Brunner captured video of the Sachatamia orejuela glass frog “waving” its arm, likely in an effort to attract a mate. This is the first time a member of the glass frog family has been observed using visual signalling. (UC Berkeley video)

Sachatamia orejuela glass frogs are native to the rainforests of Ecuador and Colombia. They are especially unique because they are almost exclusively found on rocks and boulders within the spray zones of waterfalls, where rushing water and slippery surfaces offer some protection against predators, and their green-gray color and semi-transparent skin make them nearly impossible to spot. As a result, little is known about this species’ mating and breeding behavior.

Brunner’s colleague captured a photo of her climbing a slippery rock face to film the glass frog. (Photo courtesy Rebecca Brunner)

Brunner, who studies the bioacoustics of different ecological environments, was chest-deep in an Ecuadorean rainforest stream recording the call of a Sachatamia orejuela when she first observed this visual signaling behavior. As soon as she saw the frog repeatedly raising its front and back legs, Brunner climbed a slippery rock face and balanced on one foot to get video footage of the behavior.

“I was already over the moon because I had finally found a calling male after months of searching. Before our publication, there was no official record of this species’ call, and basic information like that is really important for conservation,” Brunner said. “But then I saw it start doing these little waves, and I knew that I was observing something even more special.”

While she filmed, the frog continued to wave its hands and feet and bob its head. She also observed another male Sachatamia orejuela glassfrog a few meters away performing the same actions.

Glass frogs are named for their semi-transparent skin. (Photo courtesy Rebecca Brunner)

This is a really exhilarating discovery because it’s a perfect example of how an environment’s soundscape can influence the species that live there. We’ve found that Sachatamia orejuela has an extremely high-pitched call, which helps it communicate above the lower-pitched white noise of waterfalls. And then to discover that it also waves its hands and feet to increase its chances of being noticed —  that’s a behavior I’ve always loved reading about in textbooks, so it is beyond thrilling to be able to share another amazing example with the world,” said Brunner.

Though the COVID-19 pandemic has put a pause on Brunner’s fieldwork, she hopes to return to Ecuador soon to continue her research, which links bioacoustics and conservation.

“One of the best things about fieldwork is that nature is always full of surprises — you never know what discoveries you may happen upon,” Brunner said. “I hope our findings can serve as a reminder that we share this planet with incredible biodiversity. Conserving ecosystems that support species like Sachatamia orejuela is important not only for our well-being, but also for our sense of wonder.”

Juan M. Guayasamin, professor of biology at Universidad San Francisco de Quito, is a co-author of this research, which appears in the journal Behaviour. Brunner’s fieldwork was supported by a National Geographic Explorer Grant (EC-57058R-19) and a National Science Foundation Graduate Research Fellowship.

Reference: Rebecca M. Brunner and Juan M. Guayasamin, “Nocturnal visual displays and call description of the cascade specialist glassfrog Sachatamia orejuela”, Behavior, Volume 157: Issue 14-15, pp. 1257–1268, https://brill.com/view/journals/beh/157/14-15/article-p1257_9.xml https://doi.org/10.1163/1568539X-bja10048

Provided by University of California Berkeley

Bio-inspired Spiral Hydrogel Fiber Qualified to Be Surgical Suture (Nanotechnology)

“The lotus roots may break, but the fiber remains joined” is an old Chinese saying that reflects the unique structure and mechanical properties of the lotus fiber. The outstanding mechanical properties of lotus fibers can be attributed to their unique spiral structure, which provides an attractive model for biomimetic design of artificial fibers.

Fig 1: Biomimetic hydrogel fiber (BHF). The spiral-like structure endows BHF with excellent stretchability through plastic deformation and local failure, assisted by the breaking–reforming nature of the hydrogen bonding network among cellulose Nano fibers. © Chinese academy of sciences

In a new study published in Nano Letters, a team led by Prof. YU Shuhong from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) reported a bio-inspired lotus-fiber-mimetic spiral structure bacterial cellulose (BC) hydrogel fiber with high strength, high toughness, excellent biocompatibility, good stretchability, and high energy dissipation.

Unlike polymer-based hydrogel, the newly designed biomimetic hydrogel fiber (BHF) is based on the BC hydrogel with 3D cellulose nanofiber networks produced by bacteria. The cellulose nanofibers provide the reversible hydrogen bonding network that results in unique mechanical properties.

The researchers applied a constant tangential force to the pretreated BC hydrogel along the cross-sectional direction. Then, the two sides of the hydrogel were subjected to opposite tangential forces, and local plastic deformation occurred.

The hydrogen bonds in the 3D network of cellulose nanofibers were broken by the tangential force, causing the hydrogel strip to twist spirally and the network to slip and deform. When the tangential force was removed, the hydrogen bonds reformed between the nanofibers, and the spiral structure of the fiber was fixed.

Benefited from lotus-fiber-mimetic spiral structure, the toughness of BHF can reach ~116.3 MJ m-3, which is more than nine times higher than those of non-spiralized BC hydrogel fiber. Besides, once the BHF is stretched, it is nearly non-resilient.

Combining outstanding mechanical properties with excellent biocompatibility derived from BC, BHF is a promising hydrogel fiber for biomedical material, especially for surgical suture, a commonly used structural biomedical material for wound repair.

Compared with commercial surgical suture with higher modulus, the BHF has similar modulus and strength to soft tissue, like skin. The outstanding stretchability and energy dissipation of BHF allow it to absorb energy from the tissue deformation around a wound and effectively protect the wound from rupture, which makes BHF an ideal surgical suture.

What’s more, the porous structure of BHF also allows it to adsorb functional small molecules, such as antibiotics or anti-inflammatory compounds, and sustainably release them on wounds. With an appropriate design, BHF would be a powerful platform for many medical applications.

Reference: Qing-Fang Guan, Zi-Meng Han, YinBo Zhu, Wen-Long Xu, Huai-Bin Yang, Zhang-Chi Ling, Bei-Bei Yan, Kun-Peng Yang, Chong-Han Yin, HengAn Wu, and Shu-Hong Yu, “Bio-Inspired Lotus-Fiber-like Spiral Hydrogel Bacterial Cellulose Fibers”, Nano Letters, 2021. https://pubs.acs.org/doi/10.1021/acs.nanolett.0c03707 https://doi.org/10.1021/acs.nanolett.0c03707

Provided by Chinese Academy of Sciences

Scientists Synthetize New Material for High-Performance Supercapacitors (Material Science)

Scientists of Tomsk Polytechnic University jointly with colleagues from the University of Lille (Lille, France) synthetized a new material based on reduced graphene oxide (rGO) for supercapacitors, energy storage devices. The rGO modification method with the use of organic molecules, derivatives of hypervalent iodine, allowed obtaining a material that stores 1.7 times more electrical energy. The research findings are published in Electrochimica Acta academic journal (IF: 6,215; Q1).

Photo: modified rGO supercapacitor electrodes ©TPU

A supercapacitor is an electrochemical device for storage and release of electric charge. Unlike batteries, they store and release energy several times faster and do not contain lithium.

A supercapacitor is an element with two electrodes separated by an organic or inorganic electrolyte. The electrodes are coated with an electric charge accumulating material. The modern trend in science is to use various materials based on graphene, one of the thinnest and most durable materials known to man. The researchers of TPU and the University of Lille used reduced graphene oxide (rGO), a cheap and available material.

“Despite their potential, supercapacitors are not wide-spread yet. For further development of the technology, it is required to enhance the efficiency of supercapacitors. One of the key challenges here is to increase the energy capacity.”

It can be achieved by expanding the surface area of an energy storage material, rGO in this particular case. We found a simple and quite fast method. We used exceptionally organic molecules under mild conditions and did not use expensive and toxic metals,” Pavel Postnikov, Associate Professor of TPU Research School of Chemistry and Applied Biomedical Science and the research supervisor says.
Reduced graphene oxide in a powder form is deposited on electrodes. As a result, the electrode becomes coated with hundreds of nanoscale layers of the substance. The layers tend to agglomerate, in other words, to sinter. To expand the surface area of a material, the interlayer spacing should be increased.

“For this purpose, we modified rGO with organic molecules, which resulted in the interlayer spacing increase. Insignificant differences in interlayer spacing allowed increasing energy capacity of the material by 1.7 times. That is, 1 g of the new material can store 1.7 times more energy in comparison with a pristine reduced graphene oxide,” Elizaveta Sviridova, Junior Research Fellow of TPU Research School of Chemistry and Applied Biomedical Sciences and one of the authors of the article explains.

The reaction proceeded through the formation of active arynes from iodonium salts. They kindle scientists` interest due to their property to form a single layer of new organic groups on material surfaces. The TPU researchers have been developing the chemistry of iodonium salts for many years.

“The modification reaction proceeds under mild conditions by simply mixing the solution of iodonium salt with reduced graphene oxide. If we compare it with other methods of reduced graphene oxide functionalization, we have achieved the highest indicators of material energy capacity increase,” Elizaveta Sviridova says.

The research work was conducted with the support of the Russian Science Foundation.

Reference: Elizaveta Sviridova, Min Li, Alexandre Barras, Ahmed Addad, Mekhman S. Yusubov, Viktor V. Zhdankin, Akira Yoshimura, Sabine Szunerits, Pavel S. Postnikov, Rabah Boukherroub, “Aryne cycloaddition reaction as a facile and mild modification method for design of electrode materials for high-performance symmetric supercapacitor”, Electrochimica Acta, Volume 369, 2021, 137667, ISSN 0013-4686,
https://doi.org/10.1016/j.electacta.2020.137667.
(http://www.sciencedirect.com/science/article/pii/S0013468620320600)

Provided by Tomsk Polytechnic University

USC Study Measures Brain Volume Differences in People With HIV (Psychiatry)

Brain scans of more than 1200 HIV-infected adults across 5 continents show smaller volumes associated with lower white blood cell counts.

The shift of HIV-infection from a fatal to chronic condition in the era of more widely available treatment appears to be accompanied by a shift in the profile of HIV-related brain abnormalities beyond the basal ganglia (yellow), frequently implicated in earlier studies, to limbic structures (red). Image courtesy of Talia M. Nir, Neda Jahanshad, and James Stanis of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC.

Nearly 38 million people around the world are living with HIV, which, with access to treatment, has become a lifelong chronic condition. Understanding how infection changes the brain, especially in the context of aging, is increasingly important for improving both treatment and quality of life.

In January, researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute (USC Stevens INI), part of the Keck School of Medicine of USC, and other international NeuroHIV researchers, published one of the largest-ever neuroimaging studies of HIV. The researchers pooled magnetic resonance imaging (MRI) data from 1,203 HIV-positive individuals across Africa, Asia, Australia, Europe and North America. Their findings were published in JAMA Network Open, an open-access journal from the American Medical Association.

“Brain injury caused by HIV can lead to cognitive challenges, even in those receiving treatment,” says Talia Nir, PhD, a postdoctoral scholar at the USC Stevens INI’s Laboratory of Brain eScience (LoBeS) and first author of the study. “Establishing a common pattern of effects on the brain across different populations is a key step toward addressing those issues. The strength of this large dataset is that it is more representative of an era where treatment for HIV infection is widely available.”

The researchers looked at the link between blood plasma, which is routinely collected to monitor immune function and treatment response, and the volume of various structures in the brain. Lower white blood cell counts generally indicate that the immune system is being suppressed. Here, they found, for example, that participants with lower white blood cell counts also had less brain volume in the hippocampus and thalamus, parts of the brain’s limbic system involved in regulating memory, emotion and behavior.

These findings are important because they were largely derived from brain scans of individuals undergoing antiretroviral therapy–and they indicate that people receiving such treatment may exhibit a different brain injury signature compared to untreated individuals, which earlier studies tended to focus on. They highlight deficits in brain areas that are also vulnerable to age-related neurodegenerative diseases.

Accelerated atrophy of the hippocampus, the region that showed the most consistent effects in the study, is a hallmark of neurodegenerative diseases such as Alzheimer’s disease. Common age and HIV-related pathological processes, such as inflammation and blood brain barrier impairment, may accelerate age-related neurodegenerative processes.

“There are many factors that contribute to brain tissue loss and subsequent cognitive impairments as we age, and a person’s immune function is no exception,” says Neda Jahanshad, PhD, associate professor of neurology at the INI and one of the senior authors of the study. “Through these large-scale efforts, we’re beginning to understand the link between immune function and brain alterations in individuals living, and aging, with HIV.”

The analysis was a product of the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium’s HIV Working Group, established by Jahanshad and colleagues in 2013 to pool harmonized data across neuroimaging studies. The ENIGMA network at large, led by the institute’s associate director, Paul M. Thompson, PhD, unites neuroimaging researchers in 45 countries to study psychiatric disorders, neurodegenerative diseases and other aspects of brain function. In addition to housing ENIGMA, the USC Stevens INI is a powerhouse of neuroimaging and related science, known for large cohort analyses of imaging, genetics, behavioral, clinical and other data. Investigators from 13 existing HIV studies in the United States, France, Serbia, Australia, Thailand and South Africa collaborated on the JAMA Network Open paper.

Next, the team will analyze imaging data over time, including diffusion imaging data, another type of MRI data that maps the brain’s white matter pathways, to further understand how clinical markers of HIV infection affect the brain and the rate of neurodegeneration. As part of that ongoing work, they are inviting researchers around the world to join the ENIGMA-HIV Working Group.

“With a greater collaborative effort, we hope to be able to assess how genetic, environmental, lifestyle and treatment-related factors may further impact neurological outcomes,” Nir says.

Reference: Talia M. Nir, Jean-Paul Fouche, Jintanat Ananworanich et al., “Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV”, JAMA Netw Open. 2021;4(1):e2031190. doi:10.1001/jamanetworkopen.2020.31190 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775217

Provided by Keck School of Medicine of USC

New, Portable Device Aims to Quickly Diagnose Patients with Bleeding in Brain (Medicine)

For patients with strokes and traumatic injuries to the brain, a timely diagnosis is one of the most important factors associated with a good recovery. Current practices require a CT or MRI before beginning treatment, but a newly funded project from physicians and scientists at Keck Medicine of USC and Caltech could revolutionize rapid diagnosis and treatment for stroke and traumatic brain injury (TBI) patients.

A team of physicians and researchers from USC and Caltech received funding to develop a portable, rapid and noninvasive imaging and detection device using eddy current damping sensors that can detect brain hemorrhages associated with stroke and TBI. (Image/Courtesy Gabriel Zada)

A team of researchers led by Gabriel Zada, MD, MS, a neurosurgeon at Keck Medicine and director of the USC Brain Tumor Center, was awarded a $2.5 million National Institutes of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS) R01 grant for developing a noninvasive, handheld device to detect intracranial hemorrhage.

“For stroke patients, a major question is, is there bleeding in the brain? A CT scan or MRI can take several hours to obtain and interpret, or imagine you’re in a rural area where they have to fly you to an ER,” said Zada, professor of neurological surgery at the Keck School of Medicine of USC. “This device is portable and would be able to scan the patient’s head in the ER or field, and quickly tell if there is bleeding in the brain.”

The device uses technology developed at Caltech by Yu-Chong Tai, PhD, and adapted for use in patients by the team at USC, which also includes Nerses Sanossian, MD, director of the Roxanna Todd Hodges Stroke Program; Arthur W. Toga, PhD, director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute; and Shane Shahrestani, an MD/PhD candidate.

The portable, rapid and noninvasive imaging and detection device uses eddy current damping sensors that can detect brain hemorrhages associated with stroke and TBI. This could result in diagnosing, classifying and pinpointing the location of a hemorrhagic stroke or TBI in minutes, rather than hours. As a result, first responders and medical providers could make time-sensitive medical and surgical decisions sooner, which would improve treatment and recovery in these patients.

The grant will allow the team to further refine the device, test its ability to detect the depth and breadth of brain hemorrhage in patients, and develop algorithms to quickly and accurately classify brain lesions, as compared to CT and MRI scans.

“Our team is extremely grateful to be supported by the NIH to develop this promising technology that could change the way stroke and trauma patients are triaged and treated,” Zada said.

Provided by USC University of South California

Study: X-Rays Surrounding ‘Magnificent 7’ May Be Traces of Sought-After Particle (Astronomy)

Researchers say they may have found proof of theorized axions, and possibly dark matter, around group of neutron stars.

A new study, led by a theoretical physicist at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), suggests that never-before-observed particles called axions may be the source of unexplained, high-energy X-ray emissions surrounding a group of neutron stars.

An artistic rendering of the XMM-Newton (X-ray Multi-Mirror Mission) space telescope. A study of archival data from the XMM-Newton and the Chandra X-ray space telescopes found evidence of high levels of X-ray emission from the nearby Magnificent Seven neutron stars, which may arise from the hypothetical particles known as axions. (Credits: D. Ducros, ESA/XMM-Newton, CC BY-SA 3.0 IGO)

First theorized in the 1970s as part of a solution to a fundamental particle physics problem, axions are expected to be produced at the core of stars, and to convert into particles of light, called photons, in the presence of a magnetic field.

Axions may also make up dark matter – the mysterious stuff that accounts for an estimated 85 percent of the total mass of the universe, yet we have so far only seen its gravitational effects on ordinary matter. Even if the X-ray excess turns out not to be axions or dark matter, it could still reveal new physics.

A collection of neutron stars, known as the Magnificent 7, provided an excellent test bed for the possible presence of axions, as these stars possess powerful magnetic fields, are relatively nearby – within hundreds of light-years – and were only expected to produce low-energy X-rays and ultraviolet light.

“They are known to be very ‘boring,’” and in this case it’s a good thing, said Benjamin Safdi, a Divisional Fellow in the Berkeley Lab Physics Division theory group who led a study, published Jan. 12 in the journal Physical Review Letters, detailing the axion explanation for the excess. Christopher Dessert, a Berkeley Lab Physics Division affiliate, contributed heavily to the study, which also had participation by researchers at UC Berkeley, the University of Michigan, Princeton University, and the University of Minnesota.

If the neutron stars were of a type known as pulsars, they would have an active surface giving off radiation at different wavelengths. This radiation would show up across the electromagnetic spectrum, Safdi noted, and could drown out this X-ray signature that the researchers had found, or would produce radio-frequency signals. But the Magnificent 7 are not pulsars, and no such radio signal was detected. Other common astrophysical explanations don’t seem to hold up to the observations either, Safdi said.

If the X-ray excess detected around the Magnificent 7 is generated from an object or objects hiding out behind the neutron stars, that likely would have shown up in the datasets that researchers are using from two space satellites: the European Space Agency’s XMM-Newton and NASA’s Chandra X-ray telescopes.

Safdi and collaborators say it’s still quite possible that a new, non-axion explanation arises to account for the observed X-ray excess, though they remain hopeful that such an explanation will lie outside of the Standard Model of particle physics, and that new ground- and space-based experiments will confirm the origin of the high-energy X-ray signal.

“We are pretty confident this excess exists, and very confident there’s something new among this excess,” Safdi said. “If we were 100% sure that what we are seeing is a new particle, that would be huge. That would be revolutionary in physics.” Even if the discovery turns out not to be associated with a new particle or dark matter, he said, “It would tell us so much more about our universe, and there would be a lot to learn.”

Raymond Co, a University of Minnesota postdoctoral researcher who collaborated in the study, said, “We’re not claiming that we’ve made the discovery of the axion yet, but we’re saying that the extra X-ray photons can be explained by axions. It is an exciting discovery of the excess in the X-ray photons, and it’s an exciting possibility that’s already consistent with our interpretation of axions.”

If axions exist, they would be expected to behave much like neutrinos in a star, as both would have very slight masses and interact only very rarely and weakly with other matter. They could be produced in abundance in the interior of stars. Uncharged particles called neutrons move around within neutron stars, occasionally interacting by scattering off of one another and releasing a neutrino or possibly an axion. The neutrino-emitting process is the dominant way that neutron stars cool over time.

Like neutrinos, the axions would be able to travel outside of the star. The incredibly strong magnetic field surrounding the Magnificent 7 stars – billions of times stronger than magnetic fields that can be produced on Earth – could cause exiting axions to convert into light.

Neutron stars are incredibly exotic objects, and Safdi noted that a lot of modeling, data analysis, and theoretical work went into the latest study. Researchers have heavily used a bank of supercomputers known as the Lawrencium Cluster at Berkeley Lab in the latest work.

Some of this work had been conducted at the University of Michigan, where Safdi previously worked. “Without the high-performance supercomputing work at Michigan and Berkeley, none of this would have been possible,” he said. “There is a lot of data processing and data analysis that went into this. You have to model the interior of a neutron star in order to predict how many axions should be produced inside of that star.”

Safdi noted that as a next step in this research, white dwarf stars would be a prime place to search for axions because they also have very strong magnetic fields, and are expected to be “X-ray-free environments.”

“This starts to be pretty compelling that this is something beyond the Standard Model if we see an X-ray excess there, too,” he said.

Researchers could also enlist another X-ray space telescope, called NuStar, to help solve the X-ray excess mystery.

Safdi said he is also excited about ground-based experiments such as CAST at CERN, which operates as a solar telescope to detect axions converted into X-rays by a strong magnet, and ALPS II in Germany, which would use a powerful magnetic field to cause axions to transform into particles of light on one side of a barrier as laser light strikes the other side of the barrier.

Axions have received more attention as a succession of experiments has failed to turn up signs of the WIMP (weakly interacting massive particle), another promising dark matter candidate. And the axion picture is not so straightforward – it could actually be a family album.

There could be hundreds of axion-like particles, or ALPs, that make up dark matter, and string theory – a candidate theory for describing the forces of the universe – holds open the possible existence of many types of ALPs.

The study was supported by the U.S. Department of Energy Office of Science Early Career Research Program; Advanced Research Computing and the Leinweber Graduate Fellowship at the University of Michigan, Ann Arbor; the National Science Foundation; the Mainz Institute for Theoretical Physics (MITP) of the Cluster of Excellence PRISMA+; the Munich Institute for Astro- and Particle Physics (MIAPP) of the DFG Excellence Cluster Origins; and the CERN Theory department.

More

Excess x-rays from neutron stars could lead to discovery of new particle,” University of Minnesota, Jan. 12, 2021

New Technique Looks for Dark Matter Traces in Dark Places,” March 26, 2020

Provided by Berkeley lab

New Treatment Target Discovered That Halts Osteoarthritis-Like Knee Cartilage Degeneration (Medicine)

In a mouse study, researchers used nanotechnology and previous knowledge of a protein pathway to significantly reduce knee cartilage degeneration and pain.

There is currently no cure for osteoarthritis, but a group of scientists believe they’ve discovered a method through which a simple knee injection could potentially stop the disease’s effects. These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain. These findings were published in Science Translational Medicine.

“Our lab is one of the few in the world studying epidermal growth factor receptor (EGFR) signaling in cartilage and, from the beginning, we have found that EGFR deficiency or inactivation accelerates osteoarthritis progression in mice,” said Ling Qin, PhD, an associate professor of Orthopaedic Surgery. “Thus, we proposed that its activation could be used to treat osteoarthritis, and in this study, we’ve proven for the first time that over-activating it inside the knee blocks the progression of osteoarthritis.”

Qin explained that tests from the other labs that do work with EGFR have drawn “confusing and controversial” results. But Qin’s lab has consistently found the ties between osteoarthritis and EGFR deficiencies, which formed the bedrock of their hypothesis.

The researchers compared typical mice with those that had a molecule that bound to EGFR, called a ligand, that was over-overexpressed in chondrocytes, the building blocks of cartilage. This overexpression drives the over-activation of EGFR signaling in knee cartilage. When examining them, the mice with overexpressed HBEGF (the EGFR ligand) were found to consistently have enlarged cartilage, meaning that it wasn’t wearing away like the mice who had normal EGFR activity. Moreover, when these mice aged to adulthood, their cartilage was resistant to degeneration and other hallmarks of osteoarthritis, even if their knee’s meniscus was damaged.

To further prove that the over-activated EGFR was the reason for the mice’s resiliency, the researchers found that gefitinib treatments, which are designed to block EFGR function, took away the protection against cartilage degeneration.

With all of this knowledge gained, the researchers turned an eye toward potential clinical treatment solutions. In a new series of tests they created nanotherapeutics by attaching a potent EGFR ligand, transforming growth factor-alpha, onto synthetic nanoparticles, to inject into mice who already had cartilage damage in their knees.

“Free EGFR ligands have a short half-life and cannot be retained inside of a joint capsule due to their small size,” explained Zhiliang Cheng, PhD, a research associate professor in Penn Engineering and another of the co-corresponding authors on the paper. “Nanoparticles help to protect them from degradation, restrict them within the joint, reduce off-target toxicity, and carry them deep inside dense cartilage to reach chondrocytes.”

When mice were injected with these nanotherapeutics, the researchers saw that they slowed cartilage degeneration and bone hardening, as well as eased knee pain. There also were no major side effects seen in the mice who were treated.

“While many of the technical aspects of this application still need to be worked out, the ability to stop or slow the course of osteoarthritis with an injection rather than surgery would dramatically change how we feel and function as we age and after injury,” said one of the study’s co- authors, Jaimo Ahn, MD, PhD, a former faculty member at Penn Medicine now chief of orthopaedic trauma and associate chair of orthopaedic surgery at the University of Michigan.

The treatment is likely some time away for human patients, but the nanoparticles used have already been clinically tested and deemed safe, which makes it easier to quickly translate to clinical use.

“There is a great unmet medical need for a disease-modifying osteoarthritis drug,” Qin said. “In the future, we will optimize the drug design and test it in large animals before proceeding to clinical trials. We hope our research could lead to a novel drug that will improve the health and well-being of the more than 27 million osteoarthritis patients in the United States.”

This study was supported by the National Institutes of Health (grant numbers R01AR066098, R01DK095803, R01AG067698, P30AR069619, and R01NS100892).

Lead author on this study was Yulong Wei. Other authors included Lijun Luo, Tao Gui, Feifan Yu, Lesan Yan, Lutian Yao, Leilei Zhong, Wei Yu, Biao Han, Jay M. Patel, Jessica F. Liu, Frank Beier, L. Scott Levin, Charles Nelson, Zengwu Shao, Lin Han, Robert L. Mauck, and Andrew Tsourkas.

Reference: Yulong Wei, Lijun Luo, Tao Gui, Feifan Yu, Lesan Yan, Lutian Yao, Leilei Zhong, Wei Yu, Biao Han, Jay M. Patel, Jessica F. Liu, Frank Beier, Lawrence Scott Levin, Charles Nelson, Zengwu Shao, Lin Han, Robert L. Mauck, Andrew Tsourkas, Jaimo Ahn, Zhiliang Cheng, Ling Qin, “Targeting cartilage EGFR pathway for osteoarthritis treatment”, Science Translational Medicine  13 Jan 2021: Vol. 13, Issue 576, eabb3946 DOI: 10.1126/scitranslmed.abb3946 https://stm.sciencemag.org/content/13/576/eabb3946

Provided by Penn Medicine

About Penn Medicine

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.6 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.

NIH Scientists Identify Nutrient That Helps Prevent Bacterial Infection (Medicine)

Taurine, which helps the body digest fats and oils, could offer treatment benefit.

WHAT:

Scientists studying the body’s natural defenses against bacterial infection have identified a nutrient–taurine–that helps the gut recall prior infections and kill invading bacteria, such as Klebsiella pneumoniae (Kpn). The finding, published in the journal Cell by scientists from five institutes of the National Institutes of Health, could aid efforts seeking alternatives to antibiotics.

Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil © NIAID

Scientists know that microbiota–the trillions of beneficial microbes living harmoniously inside our gut–can protect people from bacterial infections, but little is known about how they provide protection. Scientists are studying the microbiota with an eye to finding or enhancing natural treatments to replace antibiotics, which harm microbiota and become less effective as bacteria develop drug resistance.

The scientists observed that microbiota that had experienced prior infection and transferred to germ-free mice helped prevent infection with Kpn. They identified a class of bacteria–Deltaproteobacteria–involved in fighting these infections, and further analysis led them to identify taurine as the trigger for Deltaproteobacteria activity.

Taurine helps the body digest fats and oils and is found naturally in bile acids in the gut. The poisonous gas hydrogen sulfide is a byproduct of taurine. The scientists believe that low levels of taurine allow pathogens to colonize the gut, but high levels produce enough hydrogen sulfide to prevent colonization. During the study, the researchers realized that a single mild infection is sufficient to prepare the microbiota to resist subsequent infection, and that the liver and gallbladder–which synthesize and store bile acids containing taurine–can develop long-term infection protection.

The study found that taurine given to mice as a supplement in drinking water also prepared the microbiota to prevent infection. However, when mice drank water containing bismuth subsalicylate–a common over-the-counter drug used to treat diarrhea and upset stomach–infection protection waned because bismuth inhibits hydrogen sulfide production.

Scientists from NIH’s National Institute of Allergy and Infectious Diseases led the project in collaboration with researchers from the National Institute of General Medical Sciences; the National Cancer Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Human Genome Research Institute.

Reference: A Stacy et al. Infection trains the host for microbiota-enhanced resistance to pathogens. Cell
DOI: 10.1016/j.cell.2020.12.011 (2021).

Who

Yasmine Belkaid, Ph.D., chief of NIAID’s Metaorganism Immunity Section in the Laboratory of Immune System Biology, is available to comment.

This news release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process— each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research at NIH, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Biodistribution of AAV Gene Transfer Vectors in Nonhuman Primate (Medicine)

The biodistribution of adeno-associated virus (AAV) gene transfer vectors can be measured in nonhuman primates using a new method. The method quantifies whole-body and organ-specific AAV capsids from 1 to 72 hours after administration. Study design and results are presented in the peer-reviewed journal Human Gene TherapyClick here to read the full-text article free on the Human Gene Therapy website through February 15, 2021.

Provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. Mary Ann Liebert, Inc., publishers

AAV capsids were labeled with I-124 and delivered using two routes of administration: intravenous and directly into the cerebrospinal fluid (CSF). Biodistribution was measured by quantitative positron emission tomography (PET) at 1, 24, 48, and 72 hours after AAV administration. Two AAV vectors – AAVrsh.10 and AAV9 – were compared.

“Following intravenous administration, both vectors behaved in a similar fashion, distributed primarily to the liver and to a lesser extent heart. Neither were detected at significant levels in the brain. Both vectors administered intravenously also distribute to the vertebrae,” state Ronald Crystal, Weill Cornell Medical College, and coauthors. About 50% dispersed throughout the body, in part in skeletal muscle.

Following administration into the CSF, the labeled capsid had a half-life of approximately 10 hours, suggesting the possibility of slow diffusion into the brain.

In animals with pre-existing immunity, compared to naïve animals, there was a 10-fold increase in biodistribution to the spleen.

“PET imaging is a powerful tool to track biodistribution, which is a critical property affecting the safety and efficacy of gene therapy,” according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

Research reported in this publication was supported by the National Institutes of Health under Award Number EB027918. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Reference: Douglas J. Ballon, Jonathan B. Rosenberg et al., “Quantitative Whole-Body Imaging of I-124-Labeled Adeno-Associated Viral Vector Biodistribution in Nonhuman Primates”, Human Gene Therapy, Vol. 31, No. 23-24, 2021. https://www.liebertpub.com/doi/10.1089/hum.2020.116 https://doi.org/10.1089/hum.2020.116

Provided by Mary Ann Liebert

About the Journal

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher

Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 90 journals, books, and newsmagazines is available on the  Mary Ann Liebert, Inc., publishers website.