The interactions between protons and calcium ions in this process were previously largely unknown. An article in the journal Science by a team led by biophysicist Professor Rainer Hedrich from Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, has now shed new light on this subject.

Using a sophisticated optogenetic approach, the researchers have discovered a previously unknown endogenous acid sensor in plant cells. And they have discovered in the guard cells of leaves that there is a calcium store that plays an important role in processing proton signals in cellular responses.

Why Such Simple Elements as Protons and Calcium Ions Act as Signals

In the course of evolution, cells have designed their metabolism to utilise energy-rich phosphates. This results in a problem: at the predominantly neutral cellular pH value, the valuable phosphates can be bound by calcium ions (Ca²⁺) and converted into an insoluble and therefore no longer usable form (calcium dihydrogen phosphate).

To avoid this, cells keep their internal calcium level very low; in their environment, however, it is 10,000 times higher. Outside the cells, the concentration of protons (H⁺) and therefore the acidity is also much higher. Due to this concentration gradient, both types of ions have a strong urge to flow into the cells — making them ideal for use as messenger substances.

“The stimulus-dependent opening of calcium and proton channels in the cell membrane results in a temporary intracellular increase in both messenger ions,” explains Rainer Hedrich. “The cells understand this as a signal, which they translate into a biological reaction using calcium- and proton-binding enzymes.”

Light Switch Controls the Flow of Protons Into the Cell

How do plant cells react to the influx of protons and the associated acidification of their cell plasma? Until now, this could only be investigated with great experimental effort and even then only indirectly.

This is now much easier thanks to an appropriately equipped thale cress (Arabidopsis thaliana), which Hedrich’s team has developed using optogenetic methods: A light-sensitive proton channel from a fungus, the channelrhodopsin KCR2, was optimised for use in plant cells. This means that protons can now be specifically sent into the cells in response to a light pulse.

Furthermore, they expressed KCR2 together with the genetically encoded pH reporter pHuji. This makes it very easy to measure the current pH value in the cell upon KCR2 activation.

Shouguang Huang, the first author of the Science publication, next scrutinised the guard cells of the new Arabidopsis mutant. “When I stimulated them with blue light for a second, they depolarised, just as I had expected from a light-activated proton channel,” says the researcher. During the subsequent experiments, the Würzburg ion channel specialists made a far-reaching discovery.

KCR2 Activation Acidifies the Cell and Causes Calcium to Rise

Their electrophysiological studies on guard cells showed that when the light stimulation began, the membrane potential immediately depolarised and the pH reporter pHuji signalled an acidification of the cell interior.

“However, we were astonished when the depolarisation and acidification continued for a good minute after the end of the light pulse,” says Hedrich. “This could only mean that the light activation of KCR2 and the acidification had activated the sphincter cell’s own ion channels.” These are the long-known guard cell anion channels SLAC1 and SLAH3, whose activation, however, also requires the presence of calcium.

Endoplasmic Reticulum as a Calcium Store

“Taking all the facts together, it could be assumed that the proton currents carried by KCR2 and the associated acidification of the cell interior must also have generated a calcium signal,” summarises the JMU professor.

His team was able to prove that the rapid acidification of the guard cells is followed by a calcium signal that lasts for 150 to 200 seconds. And they discovered that this calcium does not come from outside the cell, but is released from an endogenous store, the endoplasmic reticulum. This is a network of membrane tubes and cisterns that run through the cytoplasm.

Future studies will now focus on analysing the molecular nature of the H+-sensitive calcium channel of the endoplasmic reticulum and investigating its proton-activated on/off switch. Overall, these studies are important in order to better understand how plant cells react to external stimuli such as infections or drought.

It was with this in mind that the European Space Agency (ESA) launched the Gaia mission ten years ago. Data collected by the Gaia satellite are opening up a window into the near Universe, providing astronomic measurements — such as position, distance from the Earth and movement — on nearly two billion stars.

At EPFL, the Standard Candles and Distances research group headed by Prof. Richard Anderson is aiming to measure the current expansion of the Universe and sees Gaia as a valuable tool. “Gaia increased by a factor of 10,000 the number of stars whose parallaxes are measured thanks to a massive gain in accuracy over its predecessor, the ESA Hipparcos mission,” he says. Today, scientists use parallaxes to calculate the distance to stars. This method involves measuring parallax angles, with the help of the satellite, through a form of triangulation between Gaia’s location in space, the Sun and the star in question. The farther away a star, the more difficult the measurement because parallax gets smaller the larger the distance.

Despite the resounding success of Gaia, the measurement of parallax is complex, and there remain small systematic effects that must be checked and corrected in order for Gaia parallaxes to reach their full potential. This is what scientists from EPFL and the University of Bologna, in Italy, have been working on, through calculations performed on over 12,000 oscillating red giant stars* — the biggest sample size and most accurate measurements to date.

“We measured the Gaia biases by comparing the parallaxes reported by the satellite with parallaxes of the same stars that we determined using asteroseismology,” says Saniya Khan, a scientist in Anderson’s research group and the lead author of a study published today in Astronomy & Astrophysics.

Stellar earthquakes

In the same way that geologists study the Earth’s structure using earthquakes, astronomers use asteroseismology, and specifically stars’ vibrations and oscillations, to glean information about their physical properties. Stellar oscillations are measured as tiny variations in light intensity and translated into sound waves, giving rise to a frequency spectrum of these oscillations.

“The frequency spectrum lets us determine how far away a star is, enabling us to obtain asteroseismic parallaxes,” says Khan. “In our study, we listened to the ‘music’ of a vast number of stars — some of them 15,000 light-years away!”

To turn sounds into distance measurements, the research team started with a simple fact. The speed with which sound waves propagate across space depends on the temperature and density of the star’s interior. “By analyzing the frequency spectrum of stellar oscillations, we can estimate the size of a star, much like you can identify the size of a musical instrument by the kind of sound it makes — think of the difference in pitch between a violon and a cello,” says Andrea Miglio, a full professor at the University of Bologna’s Department of Physics and Astronomy and the study’s third author.

Sophisticated analyses

Having thus calculated a star’s size, the astronomers then determined its luminosity and compared this figure to the luminosity perceived here on Earth. They coupled this information with temperature and chemical-composition readings obtained from spectroscopy and ran these data through sophisticated analyses to calculate the distance to the star. Finally, the astronomers compared the parallaxes obtained in this process with those reported by Gaia in order to check the accuracy of the satellite’s measurements.

“Asteroseismology is the only way we can check Gaia’s parallax accuracy across the full sky — that is, for both low- and high-intensity stars,” says Anderson. And the future of this field is bright, as Khan outlines:

“Upcoming space missions like TESS and PLATO intended to detect and survey exoplanets will employ asteroseismology and deliver the required datasets across increasingly large regions of the sky. Methods similar to ours will therefore play a crucial role in improving Gaia’s parallax measurements, which will help us pinpoint our place in the Universe and benefit a plethora of subfields of astronomy and astrophysics.”

In the sun-soaked islands in the Caribbean, however, drought conditions can occur much more rapidly, with warning signs appearing too late for mediation strategies to limit agriculture losses or prevent stresses on infrastructure systems that provide clean water to communities.

Such occurrences — known as flash droughts — are the focus of a new paper authored by Assistant Professor Craig Ramseyer of the College of Natural Resources and Environment and published in the Journal of Hydrometeorology. The paper’s finding is that Caribbean Islands are uniquely susceptible to sudden droughts, and Ramseyer advocates for alternative methodologies to more accurately measure dry conditions in the region.

“The tropics have extremely intense solar radiation, so atmospheric processes tend to be expedited,” said Ramseyer, who teaches in the Department of Geography. “Despite often receiving daily rainfall, island ecosystems are particularly vulnerable to drought conditions.”

Ramseyer, whose research focuses on tropical rainfall and severe weather impacts in the Caribbean, utilized a new drought index that considers the atmospheric demand for moisture to identify drought risk conditions instead of more traditional soil moisture measurements.

“This new drought index is really developed to try to identify the first trigger of drought by focusing on evaporative demand,” said Ramseyer, who collaborated on the paper with Paul Miller ’12, M.S. ’14, an assistant professor at Louisiana State University. “Evaporative demand is a measure of how thirsty the atmosphere is and how much moisture it can collect from soil or plant matter.”

Ramseyer, who received funding for this research through a grant from the National Oceanic and Atmospheric Administration’s Climate Program Office, stressed that identifying drying conditions earlier is a key step to limiting the impacts of droughts.

“A lot of drought observation is based on soil moisture, but in tropical environments, a decline in soil moisture is a response to other things that have already happened so you’re further down in the chain of events,” he said. “We can mitigate a lot of losses in, say, agriculture, by being able to forecast sudden, anomalous increases in evaporative demand.”

The impacts of drought conditions extend beyond agriculture: Tropical ecosystems are also strongly impacted by dry atmospheric weather conditions, and access to fresh water is a necessity for both communities in the region and a tourism industry that is a central driver for economies in the Caribbean.

A new position for atmospheric research

To better understand how that interplay of meteorological patterns impacts drought conditions, Ramseyer utilized 40 years of data from a long-term ecological research project in the El Yunque National Forest. He found that flash droughts have routinely occurred in the Caribbean and that occurrences of drought are not limited to traditional dry seasons on the island.

“In terms of climate, Puerto Rico is situated at a crossroads, buffered on the west by the El Niño southern oscillation and by the cooler North Atlantic oscillation on the east,” said Ramseyer. “Because of that, Puerto Rico has a unique geography for researching atmospheric changes.”

The looming concerns over global warming have only accelerated the need for meteorologists to better understand drought occurrences in the Caribbean and enhance monitoring of moisture conditions in the region.

“A warming planet results in more moisture available in the atmosphere overall, which means that the kinds of short-term precipitation events common to the Caribbean will increase in intensity,” said Ramseyer. “Meanwhile, droughts are becoming higher in magnitude, so climate change is altering both extremes.”

Ramseyer, who helped secure Virginia Tech’s membership in the University Corporation for Atmospheric Research this year, said developing clearer criteria for flash drought conditions is an important first step toward addressing the infrastructure challenges that Caribbean communities are likely to face.

“The key current and future issue for the Caribbean is all about finding a way to capture rainfall successfully and draw it out slowly to mitigate evaporation losses,” said Ramseyer. “Puerto Rico and all of the Caribbean have water infrastructure challenges that must be addressed to accommodate these trends.”

Geography department chair Tom Crawford said Ramseyer’s paper reflects a utilization of big data in tackling climate and meteorological challenges.

“Dr. Ramseyer’s research applies advanced computing and geospatial science to make significant contributions to the problem of flash droughts and precipitation variability broadly,” said Crawford. “In addition to his research impact, his course on Climate Data Analysis and Programming is training the next generation of researchers on cutting edge computational techniques applied to the changing climate.”

Ramseyer advocates for additional research into understanding the relationship between flash drought events and economic losses and how future drought events can be better communicated to stakeholders and communities.

Honey bees live in dynamic communities and constantly communicate with each other using chemicals that serve as social cues. For example, nurse bees — that are responsible for taking care of larvae that ultimately become queens and worker bees — constantly monitor the larvae using in the dark using pheromones. The larvae emit brood pheromones to indicate that they need food. There are also alarm pheromones that workers produce to warn the other bees of danger. If these cues are dampened or not perceived properly, the colony may fail to thrive.

Since 2007, scientists have known that honey bees have been in trouble. One of the stressors that have raised concerns are insecticides, which affect honey bee health. Because these are usually used in combination with other chemicals, the resulting mixture can become unexpectedly toxic to bees.

“For many years, it was assumed that fungicides do not have an adverse impact on insects because they are designed for fungal targets,” said May Berenbaum (GEGC/IGOH), a professor of entomology. “Surprisingly, in addition to insecticides, fungicides also have an adverse effect on bees and combining the two can disrupt colony function.”

For more than a decade, reports originating from almond orchards, where two-thirds of the U.S. honey bees are transported every year when the flowers are in bloom, implicated pesticide spray mixtures. In particular, the problem lies in the use of supposedly inactive chemicals called adjuvants, which increases the “stickiness” of the insecticide so it stays on the plants.

Because adjuvants have long been considered to be biologically benign, they are not subject to the same level of safety testing as other insecticidal agents. “Recently, researchers have shown that adjuvants alone or when used in combination with fungicides and insecticides are toxic to bees,” Berenbaum said.

Nurse bees are especially vulnerable to these combinations. “The health of the queens is paramount,” Berenbaum said. “If healthy queens are not produced, the colony can suffer.”

To understand how combinations affect nurse bees, the researchers tested their effect on the olfactory system of honey bees using the adjuvant Dyne-Amic, the fungicide Tilt, and the insecticide Altacor.

The researchers divided bees into four groups of ten bees and for a week exposed them to either untreated commercial pollen or to pollen that had been treated with either Dyne-Amic, or Tilt and Altacor, or all three together. The bees were then anesthetized on ice and one antenna was carefully removed from each bee. The researchers then exposed the antenna to chemical mimics of brood and alarm pheromones and recorded the antenna’s response using a technique called electroantennography.

With this method, Ling-Hsiu Liao, a research scientist, and Wen-Yen Wu, a graduate student, in the Berenbaum lab, found that when nurse bees had consumed pollen contaminated by the three chemicals, their antennal responses to some brood pheromones and alarm pheromones were altered. Their finding suggests that these commonly-used pesticides can interfere with honey bee communication.

How these chemicals interact and influence the bees is still unclear. “There are many possible explanations for how consuming these chemicals can affect the sensory responses of bees,” Liao said. “The antenna detects and triggers the response to olfactory signals. In this study we did not look at what other changes are triggered, particularly changes in behavior.”

In addition to parsing out the underlying molecular pathways that are affected, the researchers are also interested in testing other mixtures of commonly used pesticides as well as looking at the response of bees in other populations. They hope that their work can help beekeepers rethink how they manage and protect their colonies.

Instead, researchers from Dartmouth and the University of St. Andrews in Scotland report that the eyes of Rudolph and his reindeer brethren may have evolved so that they can spot their favorite food during dark and snowy Arctic winters, according to a new study in the journal i-Perception.

The findings help explain the long-standing scientific mystery as to why reindeer can see light in the ultraviolet (UV) spectrum — and add intrigue to the smiling airborne ungulates popularized in the classic story by 1926 Dartmouth graduate Robert L. May.

“Reindeer are so cool, but many people think about them only at Christmas,” Nathaniel Dominy, first author of the study and the Charles Hansen Professor of Anthropology at Dartmouth says. “Now is a good time to alert people to their extraordinary visual system.”

Reindeer subsist primarily on reindeer moss, or Cladonia rangiferina, which isn’t a moss but actually a species of algae-fungus fusion known as lichen. C. rangiferina forms thick crunchy carpets across northern latitudes and is so integral to the survival of reindeer that even its formal name stems from the scientific term for reindeer, Rangifer.

The researchers worked in the Cairngorms mountains in the Scottish Highlands, which host Britain’s only reindeer herd — reintroduced from Scandinavia after being hunted to extinction locally — and more than 1,500 species of lichen. Despite these options, reindeer in the Cairngorms rely on C. rangiferina during the winter.

“A peculiar trait of reindeer is their reliance on this one type of lichen,” Dominy says. “It’s unusual for an any animal to subsist so heavily on lichens, let alone such a large mammal.”

To the human eye, the white lichen is invisible against the snowy backdrop of an Arctic winter.

But Dominy and co-authors Catherine Hobaiter and Julie Harris from St. Andrews discovered that C. rangiferina and a few other lichen species that supplement the reindeer diet absorb UV light. Spectral data from the lichen and light filters calibrated to mimic reindeer vision revealed that these organisms appear to reindeer as dark patches against an otherwise brilliant landscape, making them easier to locate.

“Getting a visual approximation of how reindeer might see the world is something other studies haven’t done before,” says Dominy, who published a paper in 2015 on how Rudolph’s red nose would’ve acted as an effective foglamp in the haze of winter.

“If you can put yourself in their hooves looking at this white landscape, you would want a direct route to your food,” he says. “Reindeer don’t want to waste energy wandering around searching for food in a cold, barren environment. If they can see lichens from a distance, that gives them a big advantage, letting them conserve precious calories at a time when food is scarce.”

Previous research has shown that reindeer eyes change between summer and winter, Dominy says. Their tapetum — the light-enhancing membrane that gives many animals “shiny” eyes — transitions in winter from the golden color most animals have to a vivid blue that is thought to amplify the low light of polar winter.

“If the color of the light in the environment is primarily blue, then it makes sense for the eye to enhance the color blue to make sure a reindeer’s photoreceptors are maximizing those wavelengths,” Dominy says.

But the blue tapetum also lets up to 60% of ultraviolet light pass through to the eye’s color sensors. That means that reindeer see the winter world as a shade of purple, similar to how a person would see a room with a black light — UV-reflecting surfaces such as snow shine brightly while UV-absorbing surfaces are starkly dark.

The researchers recount how scientists have sought to answer why the eyes of an Arctic animal that is active during the day would be receptive to the UV light that would be reflecting off of every snow-covered surface. But their study suggests that the answer is tied to what UV light doesn’t reflect from — C. rangiferina and other bushy lichens.

Given the importance of lichens in the reindeer diet, the researchers report, it is possible that the animal’s eyes are optimized to single out this food staple at the time of year it would be most difficult to find.

So, while the luminescent nose of the most famous reindeer of all “may light the way for Santa to see by,” the researchers write, “it is Rudolph’s blue eyes that allow him to find dinner after a long Christmas season.”

Joanna Marroquin, a Mason PhD in Public Health student, and Associate Professor Anna Pollack, reviewed studies conducted since 2103 that measured chemicals in menstrual products and that measured human biomarkers of chemical exposure and determined that endocrine-disrupting chemicals were found in menstrual products including tampons, pads, and liners.

“Identifying chemicals in menstrual products that menstruators regularly use is important because exposure through these products can impact menstruators’ reproductive health,” said Marroquin, the paper’s first author.

The study found that menstrual products contain a variety of endocrine-disrupting chemicals including phthalates, volatile organic compounds, parabens, environmental phenols, fragrance chemicals, dioxins and dioxin-like compounds.

This issue is even more relevant thanks to the Robin Danielson Menstrual Product and Intimate Care Product Safety Act of 2023, which was introduced in the U.S. House of Representatives in October 2023. The Act would establish a program of research regarding the risks posed by the presence of dioxins, phthalates, pesticides, chemical fragrances, and other components in menstrual products and intimate care products.

This literature reviewed 15 papers published between 2013 and 2023 that tested menstrual products in the U.S., Japan, and South Korea. The researchers note that there are few publications available that measure chemicals in menstrual products.

Additionally, though forever chemicals (PFAS) have been found in menstrual underwear, there is a lack of peer-reviewed research on menstrual underwear and other newly-popular-in-the-U.S. products such as menstrual cups and discs.

Chemicals in menstrual products: A systematic review was published in BJOG, an international journal of obstetrics and gynecology in September 2023. Additional authors include Marianthi-Anna Kiomourtzoglou from Mailman School of Public Health, Columbia University and Alexandra Scranton from Women’s Voices for the Earth.

The research was supported by Pollack’s National Institute of Environmental Health Sciences R01ES31079 award.

The study, published this week in the journal Environmental Health Perspectives, also noted an association between preconception exposure to phthalates and changes in women’s reproductive hormones, as well as increased inflammation and oxidative stress.

“Phthalates are ubiquitous endocrine disruptors and we’re exposed to them every day,” says lead author Carrie Nobles, assistant professor of environmental health sciences in the School of Public Health and Health Sciences.

Phthalates are found in such common products as shampoo, makeup, vinyl flooring, toys and medical devices. People are exposed primarily by ingesting food and liquid that has come in contact with products containing the chemicals, according to a Centers for Disease Control and Prevention fact sheet.

Nobles and team analyzed data from a “unique cohort” of women in the preconception time-to-pregnancy study known as EAGeR (Effects of Aspirin in Gestation and Reproduction), which evaluated the effect of low-dose aspirin on live-birth rates. The study includes detailed information on 1,228 participants during six menstrual cycles when they are attempting to get pregnant. The women who became pregnant were followed through pregnancy.

“We were able to look at some environmental exposures like phthalates and how that relates to how long it takes to get pregnant. There was detailed data for each menstrual cycle, so we had a good handle on the date of ovulation and the timing of pregnancy when that happened,” Nobles says.

The body breaks down phthalates into metabolites that are excreted in urine and can be analyzed. The researchers measured 20 phthalate metabolites in urine samples taken when the participants enrolled in the study.

“We found there were three parent compounds that seem to be most strongly associated with taking longer to get pregnant, although we saw a general trend toward it taking longer to get pregnant across the phthalates we looked at,” Nobles says. “As exposure got higher, we saw more and more of an effect.”

The researchers also looked at a global marker of inflammation, C-reactive protein, and found the women who had higher levels of phthalates exposure also had higher levels of inflammation and oxidative stress, which can lead to organ and tissue damage and ultimately to disease.

In addition, women who showed higher levels of phthalates had lower estradiol and higher follicle-stimulating hormone across the menstrual cycle, which play an important role in ovulation and the early establishment of pregnancy.

“This profile — estradiol staying low and follicle-stimulating hormone staying high — is actually something that we see in women who have ovarian insufficiency, which can happen with age as well as due to some other factors,” Nobles says. “Ovulation just isn’t happening as well as it used to.”

While women can check consumer product labels and look for phthalate-free options, the ubiquitous nature of the chemicals makes it difficult for an individual to control their exposure.

In Europe, certain phthalates are banned or severely restricted in their use, but the U.S. has no formal prohibitions. Nobles says the research findings add to the evidence that phthalates exposures have a negative impact on women’s reproductive health and can be used to help inform policy making.

“Maybe we want to think differently about our regulatory system and how we identify important exposures that are having adverse effects on whether people can get pregnant and have a healthy pregnancy,” Nobles says.

Over the past few decades, hydrogels have received a lot of attention for treating skin wounds. When applied over a lesion, these special gels can promote healing by absorbing discharged fluids (exudates) and keeping the wound protected, well-hydrated, and oxygenated.

However, most developed hydrogels are given adhesive properties to skin tissue to follow skin movement. Since these hydrogels are sticky and adhere to the skin and wound site, they stretch and expand the wound itself once they swell up after absorbing exudates. This not only causes pain to the user but also puts them at a higher risk of bacterial infection due to the wound area expansion. Therefore, in order to create hydrogels that can effectively treat wounds without interfering with the wound healing process, it is necessary to experiment with the preparation of hydrogels based on new ideas while utilizing existing material properties.

Against this backdrop, a team of researchers from Tokyo University of Science (TUS), Japan, have now proposed an innovative and highly-value added medical material for treating skin wounds. As reported in their recent study published in the International Journal of Biological Macromolecules, they developed a novel, low-cost hydrogel using a component found in seaweed, achieving physical properties completely different from those of conventional hydrogels. The study, which was made available online on 8 November 2023, and will be published in Volume 254, Part 3 of the journal in January 2024, was led by Mr. Ryota Teshima, a Master’s student at TUS. Assistant Professor Shigehito Osawa, Ms. Miki Yoshikawa, Associate Professor Yayoi Kawano, Professor Hidenori Otsuka, and Professor Takehisa Hanawa, all from different faculties and departments at TUS, were also a part of this study.

The method of preparation of the proposed hydrogel is quite straightforward. It was made using alginate, calcium carbonate, and carbonated water. Alginate is a biocompatible substance that can be extracted from beach-cast seaweed. Most importantly, it does not adhere strongly to cells or skin tissues. Thanks to the special structure formed by alginate and calcium ions, in addition to the protective effect of the CO₂ in carbonated water against acidification, the resulting hydrogel not only exhibited ideal pH and moisture conditions for wound recovery but also demonstrated significantly lower adhesion and swelling, compared to other commercial hydrogel wound dressings.

The researchers tested the effectiveness of their new hydrogel using cell cultures and a mouse model, both of which yielded excellent results. “Through animal experiments, we demonstrated that our hydrogel has a high therapeutic effect and at the same time can suppress the temporary expansion of the wound area caused by conventional clinical preparations,” remarks Mr. Teshima. “This proves our initial hypothesis that gels with low skin adhesion and low-swelling properties are excellent as wound dressing materials, which is the complete opposite of conventional wisdom.”

Worth noting, alginate can be extracted from beach-stranded seaweed, a renewable resource that is often regarded as a coastal waste material. Since the proposed hydrogel is not only inexpensive but also biodegradable, this development marks an important step towards future progress on sustainable medicine. “Medical materials still lack a sustainability-oriented perspective, and we believe this research will serve as a benchmark for the design of future medical materials and lead to sustainable and low-cost wound care,” says Mr. Teshima. “Moreover, our findings can help clarify issues with hydrogel formulations currently in clinical use and provide new design guidelines for next-generation wound treatment gels.”

The team used CRISPR gene editing technologies to knock out the cytoglobin gene in zebrafish. The lack of cytoglobin caused the development of embryos with a mirrored heart, meaning the heart had a reversed left-right pattern. In humans, cytoglobin is involved in processes involving nitric oxide, a compound that helps regulate healthy blood flow to organs. Study co-senior author Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, and Vice President for Medical Affairs, University of Maryland, Baltimore, has been researching the effects of nitric oxide on blood vessels for more than 20 years including in this recent study finding.

“Since its discovery two decades ago, cytoglobin has been found to be expressed in nearly all human tissues, but the mechanisms of how this protein functions were largely unknown,” said Dr. Gladwin. “We know that cytoglobin can play a role in modulating and maintaining nitric oxide levels, but our new finding indicates that it positively regulates NO production to ensure proper cilia function and its absence can lead to major laterality abnormalities of organs.”

To conduct the study, the research team knocked out the gene for cytoglobin in zebrafish and were amazed to see that it led to dramatic defects in the structure and location of organs in developing embryos. The heart, for example, was located on the right side of the fish instead of the left with a looping to the left instead of the right.

“We found that cytoglobin plays a vital role in the structure and function of tiny hair-like structures called cilia, which determine the asymmetry and proper development of organs,” said study senior author Paola Corti, PhD, Assistant Professor of Biochemistry and Molecular Biology at UMSOM.

This is the first time cytoglobin — or any of the globin proteins like hemoglobin — has been found to be involved in fetal development and that a paucity could be linked to birth defects. It’s also the first time that cytoglobin has been linked to cilia function. Such a finding could open the door for the development of therapeutics for rare birth defects that affect the movement of cilia.

About 1 in every 10,000 to 30,000 people are born with Primary Ciliary Dykinesia (PCD), a rare disease that affects the cilia and can cause breathing issues from thickened mucus clogging airways. “Kartagener’s syndrome is a form of PCD and is known to cause the type of heart defects seen in the zebrafish where the heart is abnormally positioned to the right and rotated,” said Dr. Corti. “There is no cure for this condition, just surgery to fix any heart defects and treatments to manage symptoms.”

While certain genes have been identified that are known to cause about 70 percent of PCD cases, cytoglobin could play a key role in the 30 percent of cases with no known genetic cause.

“We found the phenotype and connected the dots to cilia. In the presence of cytoglobin, we could track the function of the protein and how if led to proper cilia function and organ development. In the absence, we saw these defects,” said Elizabeth Rochon, PhD, first author of the study and Assistant Professor of Medicine at UMSOM.

Funding for the study was from the National Institutes of Health, the American Heart Association, and the Institute for Transfusion Medicine and the Hemophilia Center. UMSOM faculty co-authors include Anthony W. DeMartino, PhD, Assistant Professor of Medicine, and Qinzi Xu, MD, Assistant Professor of Medicine.

Other co-authors included faculty at the University of Pittsburgh School of Medicine and the University of Copenhagen in Denmark.