A new hypothesis about crocodile ears.

Over 1.2 billion individuals worldwide have hearing loss. Crocodiles, on the other hand, have excellent hearing for their whole lives and can live up to 70 years. One reason is that crocodiles can create new hair cells, and an Uppsala University research team is currently investigating why. Hopefully, understanding crocodile biology can benefit those who have hearing loss.

“We can see that new hair cells seem to be formed from the activation of so-called support cells, which is connected to crocodiles having certain cell structures that humans appear to lack. Our hypothesis is that nerves that carry impulses from the brain, so-called efferent nerves, trigger that regrowth,” says Helge Rask-Andersen, professor of experimental otology at Uppsala University and one of the researchers behind the study, which was recently published in the journal Frontiers in Cell and Developmental Biology.

More than a billion people worldwide have hearing loss, which causes significant difficulties for individuals and often lowers the perceived quality of life. The most common cause of hearing loss is the failure of receptors in the ears, and these receptors cannot be regenerated in humans. They may, however, be in non-mammal creatures such as crocodiles, which maintain strong hearing throughout their lives despite living up to 70 years.

It is known that animals can quickly regenerate the hair cells in their ears if they are damaged. But it is not really known how. Crocodiles have excellent hearing that is adapted for being on land and underwater. One distinctive characteristic is that the receptors’ sensitivity to different pitches is affected by external temperature, making it perfect for different kinds of dangers in different environments during evolution.

The crocodile ear has been examined in a new study by ear researchers at Uppsala University Hospital together with researchers at Uppsala University. Few research groups in the world have studied the inner ear of the crocodile, and the researchers in this study have used electron microscopy and molecular technologies.

One interesting discovery was that small cell particles are secreted in the crocodile’s ear. The particles resemble exosomes and can secrete enzymes that break down or form the membrane against which the cilia in the ear rub as sound comes in. The exosomes form small alveoli, cavities, that make it easier for the cilia to bend when sound vibrations reach the ear.

“One hypothesis is that this increases sensitivity to sound and hearing improves. Our hope is to learn how crocodiles regenerate their hair cells and to eventually be able to use that on people in the future,” says Helge Rask-Andersen.

Reference: “Regeneration in the Auditory Organ in Cuban and African Dwarf Crocodiles (Crocodylus rhombifer and Osteolaemus tetraspis) Can We Learn From the Crocodile How to Restore Our Hearing?” by Hao Li, Karin Staxäng, Monika Hodik, Karl-Gunnar Melkersson, Mathias Rask-Andersen and Helge Rask-Andersen, 4 July 2022, Frontiers in Cell and Developmental Biology.
DOI: 10.3389/fcell.2022.934571

The study found that pairing Spinraza® with valproic acid could boost its effects.

A New Drug Duo

Spinraza® changed the game for people with spinal muscular atrophy (SMA) in 2016. It was the first medication for the neurodegenerative condition that is the leading genetic cause of infant mortality to get FDA approval. Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer and colleagues conceptualized and developed the medication.

Krainer didn’t stop there, however. Together with Alberto Kornblihtt at the Universidad de Buenos Aires, his lab has been looking into whether Spinraza® could be enhanced. They identified a novel strategy to enhance the therapeutic benefits of Spinraza® by combining it with valproic acid (VPA), a separate FDA-approved drug.


Increasing a drug’s dose is one method for increasing its impact. But like with any drug, using more Spinraza® puts you at risk for negative side effects. Krainer and his associates used a different strategy. They found that combining Spinraza® with VPA could be an alternative method for increasing its clinical effect without using more of the drug. Krainer explains:

“Sometimes you don’t want to use a ton of a drug. If you have a condition that allows you to use less of the drug, then you may have fewer toxicities. So the idea is to combine these two drugs to get maximal effects.”

People with SMA don’t have enough of a protein called SMN. Spinraza® is a type of molecule called an antisense oligonucleotide (ASO) that helps cells make more SMN protein from a gene called SMN2. The team discovered that there were roadblocks on the SMN2 gene when using Spinraza®. This slowed down the cellular machine producing SMN protein. The drug VPA helps remove the roadblocks, allowing Spinraza® to further increase the SMN protein output. When mice with SMA were treated with both VPA and a Spinraza®-like ASO used for research, the mice survived longer and had improved muscle function.


Over 11,000 SMA patients have been treated with Spinraza® in more than 50 countries. Krainer’s latest research shows that there’s always room for improvement. He hopes the team’s findings will help optimize the efficacy of Spinraza® treatments. He also hopes their work will help researchers who are trying to develop therapies for other neurodegenerative diseases.

Reference: “Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy” by Luciano E. Marasco, Gwendal Dujardin, Rui Sousa-Luís, Ying Hsiu Liu, Jose N. Stigliano, Tomoki Nomakuchi, Nick J. Proudfoot, Adrian R. Krainer and Alberto R. Kornblihtt, 9 June 2022, Cell.
DOI: 10.1016/j.cell.2022.04.031

The study was funded by Familias Atrofia Muscular Espinal, CureSMA, Richard Lounsbery Foundation, Universidad de Buenos Aires, Agencia Nacional de Promoción Científica y Tecnológica of Argentina, NIH/National Institutes of Health, Consejo Nacional de Investigaciones Científicas y Técnicas, St. Giles Foundation, Fundação para Ciência e a Tecnologia.

A graphic of traumatic brain injury with blood test vials. Credit: Justine Ross, Michigan Medicine

In the study, the method predicted poor outcomes six months after injury with high accuracy.

A study finds that blood tests taken the day of a traumatic brain injury (TBI) can accurately predict which patients are likely to die or survive with severe disability. This could allow clinicians to make decisions earlier on possible treatment of TBI. 


Researchers analyzed day-of-injury blood tests of nearly 1,700 patients with TBI. Results reveal that higher values of two protein biomarkers, GFAP and UCH-L1, are associated with death and severe injury. The study, from Michigan Medicine, the University of California San Francisco, and the University of Pennsylvania, was published in The Lancet Neurology.

According to first author Frederick Korley, M.D., Ph.D., this is the first study to examine the association between biomarker levels of these two proteins and all-cause mortality following TBI. Korley is an associate professor of emergency medicine at the University of Michigan Medical School.

“Early and accurate prediction of TBI outcomes will help clinicians gauge how severe a brain injury is and inform how best to counsel family members about care for their loved ones with brain injury and what to expect with regards to their recovery,” Korley said. “It will also help researchers more precisely target promising TBI therapeutics to the right TBI patients.”


The U.S. Food and Drug Administration (FDA) cleared the use of GFAP and UCH-L1 in 2018 to help clinicians decide whether to order CT scans for mild traumatic brain injury.

Scientists measured the proteins using two devices from Abbott Laboratories, the i-STAT Alinity, and the ARCHITECT. Results were compared to evaluations made six months after injury using the Glasgow Outcome Scale-Extended, a system that grades the functional status of TBI patients.

Investigators found that compared to those with GFAP values in the bottom 20th percentile, those with GFAP values in the top 20th percentile had a 23 times higher risk of death during the subsequent six months. Similarly, compared to those with UCH-L1 values in the bottom 20th percentile, those with UCH-L1 values in the top 20th percentile had a 63 times higher risk of death during the subsequent 6 months.

“Modern trauma care can result in good outcomes in what we had once believed were non-survivable injuries,” said co-senior author Geoffrey Manley, M.D., Ph.D., professor and vice chair of neurosurgery at UCSF. “These blood tests are both diagnostic and prognostic, as well as easy to administer, safe and inexpensive.”


While the method is promising for determining poor outcomes in moderate and severe TBI, researchers say more must be done to examine its role in mild cases.

“As a next step, the TRACK-TBI team is planning a clinical trial that will examine the efficacy of promising therapeutic agents that may help traumatic brain injury patients recover quickly,” Korley said. “As part of this clinical trial, these biomarkers will be used as an objective method for selecting the right patients to enroll in this trial. We will also use these biomarkers to monitor individual patient response to these promising therapeutics.”

Reference: “Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study” by Frederick K Korley, MD PhD; Prof Sonia Jain, PhD; Xiaoying Sun, MS; Ava M Puccio, PhD; John K Yue, MD; Raquel C Gardner, MD; Prof Kevin K W Wang, PhD; Prof David O Okonkwo, MD PhD; Prof Esther L Yuh, MD PhD; Prof Pratik Mukherjee, MD; Lindsay D Nelson, PhD ABPP-CN; Sabrina R Taylor, PhD; Amy J Markowitz, JD; Prof Ramon Diaz-Arrastia, MD PhD; Prof Geoffrey T Manley, MD PhD and the TRACK-TBI Study Investigators, 1 September 2022, The Lancet Neurolog.
DOI: 10.1016/S1474-4422(22)00256-3

Korley previously consulted for Abbott Laboratories. Korley and Robertson have received research funding from Abbott Laboratories. Manley received research funding from a collaboration between Abbott Laboratories and the U.S. Department of Defense. Diaz-Arrastia consulted for MesoScale Discoveries, BrainBox Solutions, and NovaSignal. All other authors and collaborators declare no competing interests.

Researchers discovered new compounds in marine sponges that were capable of killing antibiotic-resistant bacteria.

Brazilian scientists discovered several compounds in a marine sponge from Fernando de Noronha, an island off the coast of the Northeast, that killed antibiotic-resistant bacteria.

Researchers at the University of So Paulo (USP) in So Carlos, Brazil, have identified a variety of bioactive substances in a marine sponge that was found on Fernando de Noronha, an island located about 400 km off the northeastern coast of Brazil. Some of the substances were able to kill bacteria that are resistant to current antibiotics, opening the door for the creation of new medications.


The study was funded by FAPSEP and its findings were published in the Journal of Natural Products.

“This marine sponge had been studied previously by groups outside Brazil, mainly in the 1990s. We used next-generation techniques to analyze substances from their secondary metabolism, look for new molecules, and test their biological activity. We were able to describe a number of novel compounds. The main potential detected was against drug-resistant bacteria,” said Vítor Freire, who conducted the study as part of his Ph.D. research at the São Carlos Institute of Chemistry (IQSC-USP).

Several substances that killed antibiotic-resistant bacteria were found by Brazilian researchers in a marine sponge native to Fernando de Noronha, an archipelago off the coast of the Northeast. Credit: Eduardo Hajdu/Museu Nacional/UFRJ

The World Health Organization (WHO) views antibiotic resistance as a serious worldwide public health issue. An analysis commissioned by the British government and released in 2016 predicted that in 2050, there would be 10 million drug-resistant bacterial infection-related fatalities annually. Therefore, it is crucial to develop new, powerful antibiotics.

Agelas dispar, a species endemic to the Caribbean and a portion of the Brazilian coast, is the marine sponge that was the subject of the study’s analysis. Marine sponges spend their whole lives attached to reefs or the ocean floor and are some of the oldest animals on Earth. They have evolved a sophisticated metabolism during millions of years of evolution, generating substances needed for competition with other invertebrates and defense against dangerous bacteria.

The substances with the most therapeutic potential identified in the study were three different types of ageliferin, named after the marine sponge genus Agelas.

“Another important factor is the ability of sponges to store symbiont microorganisms, which also help them defend themselves. When we analyze compounds found in sponges, we don’t always know what’s been produced by them and what comes from symbionts,” said Roberto Berlinck, a professor at IQSC-USP and principal investigator for the study.


The research was conducted as part of two projects led by Berlinck and supported by FAPESP.

The trials involving bacteria were performed at Adolpho Lutz Institute (IAL), the reference laboratory for epidemiological surveillance in São Paulo state, and led by André Gustavo Tempone, a researcher also supported by FAPESP.

Tumors and bacteria

Thirteen compounds were tested on an ovarian cancer cell line known as OVCAR3 but were not found to be biologically active. Other research groups that tested ageliferins on lung, colon and breast cancer cells did not observe anti-tumor action, and one had no effect on lymphoma cells. However, three ageliferins eliminated drug-resistant bacteria Escherichia coli and Enterococcus faecalis, which are extremely common and found in various environments as well as the human body; and Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, listed by WHO as priority targets for novel antibiotics and among the bacteria responsible for most hospital-acquired infections.

The researchers wanted to know whether the use of these ageliferins could lead to the destruction of red blood cells (hemolysis) in the intestines, a potentially lethal side effect often seen in patients undergoing chemotherapy who need antibiotics. In murine cells, the compounds did not cause this kind of damage, suggesting promising drug development potential.


The next step is to analyze other marine sponges using the same methodology. “Finding out how these substances are produced is extremely important as they’re distributed by several classes of sponge and could help treat diseases in the future,” said Freire, currently a postdoctoral researcher at the National Cancer Institute in the United States.

Reference: “Feature-Based Molecular Networking Discovery of Bromopyrrole Alkaloids from the Marine Sponge Agelas dispar” by Vítor F. Freire, Juliana R. Gubiani, Tara M. Spencer, Eduardo Hajdu, Antonio G. Ferreira, Dayana A. S. Ferreira, Erica V. de Castro Levatti, Joanna E. Burdette, Carlos Henrique Camargo, Andre G. Tempone and Roberto G. S. Berlinck, 15 April 2022, Journal of Natural Products.
DOI: 10.1021/acs.jnatprod.2c00094

The study was funded by the São Paulo Research Foundation.

Artist’s illustration of a pulsar. Credit: Carl Knox, OzGrav-Swinburne University

Occasionally pulsars—rapidly-spinning remnants of stars that flash like a lighthouse—show extreme variations in brightness. Astrophysicists predict that these short bursts of brightness occur because dense regions of interstellar plasma (the hot gas between stars) scatter the radio waves emitted by the pulsar. However, we still don’t know where the energy sources required to form and sustain these dense plasma regions come from. To better understand these interstellar formations, more detailed observations of their small-scale structure are required. A promising avenue for this is in the scintillation, or “twinkling,” of pulsars.

When a pulsar’s radio waves are scattered by the interstellar plasma, the separate waves interfere and create an interference pattern on the Earth. As the Earth, pulsar, and plasma move relative to each other, this pattern is observed as brightness variations in time and in frequency: the dynamic spectrum. This is scintillation, or “twinkling.” The scattering and twinkling occurs in small regions of the plasma thanks to the point-like nature of pulsar signals. Following specialized signal processing of the dynamic spectrum, we can observe vivid parabolic features known as scintillation arcs that are related to the image of the pulsar’s scattered radiation on the sky.


One particular pulsar, called J1603-7202, underwent extreme scattering in 2006. This makes it an exciting target for examining these dense plasma regions. However, the pulsar’s trajectory still hasn’t been determined as it orbits another compact star called a white dwarf in a face-on orbit, and astronomers don’t have alternative methods to measure it in this situation. Fortunately, scintillation arcs serve a double purpose: their curvatures are related to the pulsar’s velocity, as well as the distance to the pulsar and the plasma. How the pulsar’s velocity changes as it orbits depends on the orbit’s orientation in space. Therefore, in the case of pulsar J1603-7202, we calculated the changes in the curvature of the arcs over time to determine the orientation.

The measurements we obtained for the orbit of pulsar J1603-7202 are a significant improvement compared to previous analyses. This demonstrates the viability of scintillation in supplementing alternative methods. We measured the distance to the plasma and showed that it was about three-quarters of the distance to the pulsar, from Earth. This does not seem to coincide with the positions of any known stars or interstellar gas clouds. Pulsar scintillation studies often explore structures such as this, which are otherwise invisible. The question, therefore, remains open: what is the source of the plasma that scatters the pulsar’s radiation?

Finally, using our orbit measurement, we are able to estimate the mass of J1603-7202’s orbital companion. It was calculated to be about half the mass of the Sun. When considered alongside the highly circular orbit of J160-7202, this implies the companion is likely a stellar remnant composed of carbon and oxygen — a rarer find around a pulsar than the more common helium-based remnants.


As we now possess a near-complete model of the orbit, it’s currently possible to transform scintillation observations of J1603-7202 into on-sky scattered images and map the interstellar plasma at Solar System scales. Creating images of the physical structures that cause extreme scattering of radio waves may give us a better understanding of how such dense regions form and of the role the interstellar plasma plays in the evolution of galaxies.

Written by PhD student Kris Walker (ICRAR-UWA) and Dr. Daniel Reardon (OzGrav-Swinburne University).

Reference: “Orbital Dynamics and Extreme Scattering Event Properties from Long-term Scintillation Observations of PSR J1603−7202” by Kris Walker, Daniel J. Reardon, Eric Thrane and Rory Smith, 28 June 2022, The Astrophysical Journal.
DOI: 10.3847/1538-4357/ac69c6

The most common kind of heart disease in the US is coronary artery disease (CAD), which can result in a heart attack.

Discriminatory housing policies from the past may still have an impact on heart disease risk factors and outcomes today.

More than 60 years after they were outlawed, the historical discriminatory housing practices known as “redlining” are still connected to heart disease and related risk factors in the affected districts, according to a study recently published in the Journal of the American College of Cardiology. Health disparities have been related to a number of socioeconomic, environmental, and social variables. This research adds to the increasing body of evidence demonstrating the long-term cardiovascular impacts disparities may have on vulnerable groups.

The phrase “redlining” is used to refer to a variety of discriminatory housing practices. Its roots are in a government program from the 1930s when the Home Owners’ Loan Corporation produced maps of over 200 American towns with ratings based on racial/ethnic mix, housing conditions, and local surroundings.


The graded locations were color-coded as A (“best” or green), B (“still desirable” or blue), C (“definitely declining” or yellow), and D (“hazardous” or red) depending on the potential lending risk. The areas with a D-rating were referred to as “redlined” areas. Despite the fact that these housing practices were prohibited in the 1960s, throughout the course of the last century, their consequences and other forms of discrimination have persisted to shape social and environmental structures, worsening health inequities.

“We already know historic redlining has been linked with modern-day health inequities in major urban areas, including asthma, certain types of cancer, preterm birth, mental health, and other chronic diseases,” said Sadeer Al-Kindi, MD, a cardiologist at University Hospitals Harrington Heart & Vascular Institute and Assistant Professor of Medicine at Case Western Reserve University in Cleveland and a senior author on the study. “While ours is the first study to examine the national relationship between redlined neighborhoods and cardiovascular diseases, it’s logical that many of the socioeconomic, environmental, and social impacts of redlining on other areas of residents’ health outcomes would also be seen in heart disease.”

A previous study demonstrated that Black adults living in historically redlined areas had a lower cardiovascular health score than Black adults living in A-graded neighborhoods. The current study supports this finding and extends the demonstrated health inequality nationally, showing that redlining not only affects coronary artery disease, stroke, and chronic kidney disease but also is associated with an increased risk of comorbidities and a lack of access to appropriate medical care.


The researchers used original Home Owners’ Loan Corporation (HOLC) graded data and calculated the percentage of intersection between each graded neighborhood boundary and the 2020 U.S. Census tract boundaries. They excluded any census tracts with less than 20% total area of intersection. The researchers used the graded intersections to generate a scale using their corresponding HOLC numeric scores (1-4 corresponding to A-D) and created a score that was transformed back into one of four categories: A (1), B (2), C (3) and D (4). The study defined redlined neighborhoods as D-graded census tracts and non-redlined neighborhoods as A- through C-graded census tracts.

The CDC PLACES database, which reports the prevalence estimates of census tract level health indicators, as well as census-tract level exposure of particulate matter and Diesel particulate matter from the Environmental Protection Agency’s 2021 environmental justice tool, were used to calculate potential environmental confounders. Other outcome variables and assessments used included: markers of health care access, cardiometabolic risk factors, and cardiometabolic outcomes. The researchers then linked HOLC-graded census tracts with the prevalence of cardiometabolic indicators and calculated the average of each indicator across census tracts in each HOLC grade.

More than 11,000 HOLC-graded census tracts were included, comprising over 38.5 million inhabitants. The A-graded areas covered 7.1%, B-graded areas covered 19.4%, C-graded areas covered 42% and D-graded areas covered 31.5% of census tracts. The percentage of Black and Hispanic residents increased across HOLC grades (A-D, respectively). Across HOLC grades A through D, the researchers found statistically significant increases in the prevalence of coronary artery disease, stroke, and chronic kidney disease.

“We found neighborhoods with so-called better HOLC grades had higher cholesterol screening and routine health visits when compared to neighborhoods with worse HOLC grades. And the prevalence of adults 18 to 64 years old without health insurance nearly doubled from A through D-graded areas,” said Issam Motairek, MD, lead author of the study and a clinical research associate at University Hospitals Harrington Heart & Vascular Institute in Cleveland. “In each stepwise increase across the HOLC grading spectrum, from A to D, we also observed an overall increase in rates of diabetes, obesity, hypertension, and smoking.”


According to the researchers, the association between redlining and the prevalence of cardiometabolic conditions further illustrates that historic redlining practices may impact contemporary cardiovascular outcomes by traditional and non-traditional risk factors. Residents of redlined neighborhoods, particularly minorities, are known to have lower access to public transportation, health care insurance, and healthy food choices, which increases their risk for missed prevention and adverse health outcomes.

Disparities in environmental exposures and in socioeconomic attributes may help explain the poor health outcomes in redlined neighborhoods, which are often situated next to major sources of pollution and make residents more likely to experience the detrimental health effects of disproportionately higher exposure to air pollution, less green space and other environmental toxins. Residents of redlined neighborhoods also experience financial strain, dismantled communities, and racial discrimination which may lead to increased stress and associated adverse health events.

Study limitations include self-reported health outcomes in the CDC PLACES database, which may be mischaracterized. The study was also unable to measure confounders such as behavioral and genetic factors. The definition of redlining census tract boundaries has also not been standardized across studies.

Reference: “Historical Neighborhood Redlining and Contemporary Cardiometabolic Risk” by Issam Motairek, Eun Kyung Lee, Scott Janus, Michael Farkouh, Darcy Freedman, Jackson Wright, Khurram Nasir, Sanjay Rajagopalan and Sadeer Al-Kindi, 4 July 2022, Journal of the American College of Cardiology.
DOI: 10.1016/j.jacc.2022.05.010