When birch trees are grown in highly polluted areas, their pollen contains higher levels of the main allergen, according to Polish study

Peer-Reviewed Publication

PLOS

 

IMAGE: BIRCH TREES. view more 

CREDIT: DOROTA MYSZKOWSKA, CC-BY 4.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/4.0/)

Article URL:  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279826

Article Title: Air pollution in the places of Betula pendula growth and development changes the physicochemical properties and the main allergen content of its pollen

Author Countries: Poland

Funding: The study was supported by the grant of the National Science Centre, No2016/21/N/NZ8/01369. Grant holder was the corresponding author: Monika Ziemianin. The FT-Raman measurements were financed by DNWZ.711.58.2022.PBU statutory research project of Pedagogical University of Krakow, Poland, led by Ph.D. Iwona Stawoska. In both cases, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0279826 

ARTICLE TITLE

Air pollution in the places of Betula pendula growth and development changes the physicochemical properties and the main allergen content of its pollen

ARTICLE PUBLICATION DATE

25-Jan-2023

52-million-year-old fossils show near-primates were cool with colder climate

The fossils were discovered on Ellesmere Island, Nunavut, Canada, in layers of sediment linked with the early Eocene, an epoch that could foretell how ecosystems will fare in coming years

Peer-Reviewed Publication

UNIVERSITY OF KANSAS

 

IMAGE: ARTIST'S RECONSTRUCTION OF IGNACIUS DAWSONAE SURVIVING SIX MONTHS OF WINTER DARKNESS IN THE EXTINCT WARM TEMPERATE ECOSYSTEM OF ELLESMERE ISLAND, ARCTIC CANADA. view more 

CREDIT: KRISTEN MILLER, BIODIVERSITY INSTITUTE, UNIVERSITY OF KANSAS

LAWRENCE — Two sister species of near-primate, called “primatomorphans,” dating back about 52 million years have been identified by researchers at the University of Kansas as the oldest to have dwelled north of the Arctic Circle. The findings appear today in the peer-reviewed journal PLOS ONE.

According to lead author Kristen Miller, doctoral student with KU’s Biodiversity Institute and Natural History Museum, both species — Ignacius mckennai and I. dawsonae — descended from a common northbound ancestor who possessed a spirit “to boldly go where no primate has gone before.”

The specimens were discovered on Ellesmere Island, Nunavut, Canada, in layers of sediment linked with the early Eocene, an epoch of warmer temperatures that could foretell how ecosystems will fare in coming years due to human-driven climate change.

“No primate relative has ever been found at such extreme latitudes,” Miller said. “They’re more usually found around the equator in tropical regions. I was able to do a phylogenetic analysis, which helped me understand how the fossils from Ellesmere Island are related to species found in midlatitudes of North America — places like New Mexico, Colorado, Wyoming and Montana. Even down in Texas we have some fossils that belong to this family as well.”

The Arctic Circle was much warmer when these close evolutionary cousins of primates lived — a boreal ecosystem that hosted a plethora of early Cenozoic vertebrates, including ancient crocodiles — but like today was still mostly dark for half of the year. This darkness, according to Miller, may have triggered both species to evolve more robust teeth and jaws compared with other primate relatives of the time.

“A lot of what we do in paleontology is look at teeth — they preserve the best,” said Miller, who analyzed high-resolution microtomography of the fossil teeth described in the paper. “Their teeth are just super weird compared to their closest relatives. So, what I've been doing the past couple of years is trying to understand what they were eating, and if they were eating different materials than their middle-latitude counterparts.”

Miller and her co-authors believe food was much tougher to find during dim winter months when the Artic primate relatives likely were forced to consume harder material.

“That, we think, is probably the biggest physical challenge of the ancient environment for these animals,” said corresponding author Chris Beard, senior curator of vertebrate paleontology at the Biodiversity Institute and Foundation Distinguished Professor of Ecology & Evolutionary biology at KU. “How do you make it through six months of winter darkness, even if it's reasonably warm? The teeth and even the jaw muscles of these animals changed compared to their close relatives from midlatitudes. To survive those long Arctic winters, when preferred foods like fruits were not available, they had to rely on 'fallback foods' like nuts and seeds.”

Miller and Beard’s other co-author is Kristen Tietjen, a scientific illustrator at the Biodiversity Institute. 

Additionally, the researchers found both species were slightly larger than their closest relatives farther to the south — a group of primate cousins dubbed “plesiadapiforms.”

“But they're still pretty small,” Miller said. "Some plesiadapiforms from the midlatitudes of North America are really, really tiny. Of course, none of these species are related to squirrels, but I think that's the closest critter that we have that helps us visualize what they might have been like. They were most likely very arboreal — so, living in the trees most of the time.”

The researchers think adaptations displayed by both Arctic species during a time of global warming show how some animals likely could evolve new traits in response to climate change driven by human activity today.

“It does show how something like a primate or a primate relative that’s specialized to one environment can change based off of climate change,” Miller said. “I think probably what it says is primates’ range could expand with climate change or move at least towards the poles rather than the equator. Life starts to get too hot there, perhaps we’ll have a lot of taxa moving north and south, rather than the intense biodiversity we see at the equator today.”

Because both fossil species are new to science, the investigators bestowed them with scientific names honoring a pair of paleontologists who worked on Ellesmere Island decades ago. One of these namesake paleontologists was a KU alumna and pioneer for women in the field of paleontology.

“Mary Dawson was an amazing person,” Beard said. “She earned her doctorate at KU back in the '50s and was among the first, if not the first, American women to get a Ph.D. in paleontology — and one of the first women to make a name for herself as a paleontologist in the United States. I worked closely with Mary for more than 20 years in my former career at the Carnegie Museum, where she spent her whole career. Mary was the leader of a big project on Ellesmere Island. Of course, we were going to name one of the species after her. The other species is named after Malcolm McKenna, a contemporary, close friend and colleague of Mary Dawson and a former mentor of mine.”

Indeed, the fossil species Ignacius mckennai and I. dawsonae were part of a collection of fossils left behind by Dawson and McKenna for further analysis.

“Mary and Malcolm bequeathed me with those fossils and asked me to study them,” Beard said. “I said, ‘Yes, of course — I'm happy to do that.’ They just sat like a fine wine and got better and better through time until Kristen showed up — and it was clear that Kristen had everything that it took to carry the ball over the finish line.”

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0280114 

ARTICLE TITLE

Basal Primatomorpha colonized Ellesmere Island (Arctic Canada) during the hyperthermal conditions of the Early Eocene Climatic Optimum

SEE 

https://plawiuk.blogspot.com/2023/01/bigfoot-yeti-sasquatch-fossils-reveal.html

THIRD WORLD U$A

Heart failure risk higher in rural areas

Peer-Reviewed Publication

VANDERBILT UNIVERSITY MEDICAL CENTER

 

IMAGE: LOREN LIPWORTH, SCD, PROFESSOR OF MEDICINE AND ASSOCIATE DIRECTOR OF THE DIVISION OF EPIDEMIOLOGY view more 

CREDIT: VANDERBILT UNIVERSITY MEDICAL CENTER

Heart failure risk is 19% higher for adults living in rural areas of the U.S., as compared to urban areas, and 34% higher for Black men living in rural areas, according to a large, observational study supported by the National Institutes of Health (NIH) and co-led by Vanderbilt University Medical Center (VUMC) researchers.

 

The study, one of the first to look at the link between first-time cases of heart failure and patients living in rural areas, was published today in JAMA Cardiology. 

 

“The study demonstrates the relationship between rurality and the occurrence of heart failure and is the first to do so in a predominantly low-income population of Black and white adults residing in the southeastern U.S.,” said Loren Lipworth, ScD, professor of Medicine and associate director of the Division of Epidemiology, who co-led the study for VUMC along with Deepak Gupta, MD, associate professor of Medicine and director of the Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular Medicine.

 

Researchers from the National Heart, Lung, and Blood Institute (NHLBI) – which is part of the NIH – and VUMC analyzed data from The Southern Community Cohort Study, comparing rates of new onset heart failure among rural and urban residents in 12 states (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia). 

 

The population, which included 27,115 adults without heart failure at enrollment, were followed for about 13 years. Nearly 20% of participants lived in rural areas and roughly 69% were Black adults recruited from community health centers that care for medically underserved populations.



 

At the end of the study period, the researchers found that rurality was associated with an increased risk of heart failure among both women and Black men, even after adjustment for other cardiovascular risk factors and socioeconomic status. 

 

The study showed white women living in rural areas had a 22% increased risk of heart failure compared to white women in urban areas, and Black women had an 18% higher risk compared to Black women in urban areas. 

 

No association was found between rurality and heart failure risk among white men.

 

“Our findings in the Southern Community Cohort Study highlight race- and sex-based inequities in heart failure risk that have important implications for the primary prevention of heart failure, including a need to focus on community or contextual factors that may preferentially impact women or Black men living in rural areas,” Lipworth said.

 

Heart failure, which affects an estimated 6.5 million adults in the U.S., develops when the heart does not pump enough blood for the body’s needs or requires higher pressure to do so. Its symptoms may include shortness of breath during daily activities or trouble breathing when lying down, among others. Patients with heart failure often have lower quality of life and shorter survival, which raises the importance of preventing heart failure.  

 

“Approximately 1 million new cases of heart failure are diagnosed in the U.S. each year,” Gupta said. “Our findings demonstrate substantial variability in susceptibility to heart failure. The results not only emphasize the importance of identifying these differences but also suggest heart failure prevention may require varied approaches across individuals.  

 

“As Vanderbilt is a leader in precision medicine, our next step should be to translate these observational findings into targeted interventions to prevent heart failure, particularly among individuals who bear a disproportionate burden of risk,” he added.   

 

The exact reasons behind these rural-urban health disparities are unclear and are still being explored. But the researchers said a multitude of factors may be at play, including structural racism, inequities in access to health care, and a dearth of grocery stores that provide affordable and healthy foods, among others. 

 

The study was funded by the NIH Medical Research Scholars Program; NHLBI’s Division of Intramural Research; the NHLBI Training Award in Cardiovascular Research (T32 367 HL007411); the Intramural Research Program of the National Institute on Minority Health and Health Disparities; the National Cancer Institute (grants R01 CA092447 and 368 U01 CA202979); and supplemental funding from the American Recovery and Reinvestment Act (3R01 CA 029447-0851). 

 

Other VUMC co-authors include Meng Xu, Debra Dixon, and Michael Mumma.

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JOURNAL

JAMA Cardiology

DOI

10.1001/jamacardio.2022.5211 

ARTICLE TITLE

Association of rurality with risk of heart failure

ARTICLE PUBLICATION DATE

25-Jan-2023

Kill dates for re-exposed black mosses

New Geology Science published online ahead of print

Peer-Reviewed Publication

GEOLOGICAL SOCIETY OF AMERICA

 

IMAGE: CAPE RASMUSSEN, ONE OF THE STUDY SITES MENTIONED IN THE PAPER. CREDIT: DEREK J. FORD. view more 

CREDIT: DEREK J. FORD

Boulder, Colo., USA: In their new paper for the Geological Society of America journal Geology, Dulcinea Groff and colleagues used radiocarbon ages (kill dates) of previously ice-entombed dead black mosses to reveal that glaciers advanced during three distinct phases in the northern Antarctic Peninsula over the past 1,500 years.

The terrestrial cryosphere and biosphere of the Antarctic Peninsula are changing rapidly as “first responders” to polar warming. We know from other studies that large glaciers of the Antarctic Peninsula are responding quickly to warmer summer air temperatures, and scientists have modeled that the glaciers expanded in the past because of cooler temperatures, and not increased precipitation. However, we know much less about how this plays out at sea level where ice, ocean, and sensitive coastal life interact. Knowing when glaciers advanced and retreated in the past would improve our understanding of biodiverse coastal ecosystems—thriving with seals, penguins, and plants—and their sensitivity in the Antarctic Peninsula. One of the limitations of reconstructing glacier history is that there are not that many types of terrestrial archives we can use to constrain past glacier behavior. Re-exposed dead plants, abandoned penguin colonies, and rocks can be dated to better know the timing of permanent snow or glacier advance in the past.

Mosses are one of the few types of plants living in Antarctica and can get overridden and killed by advancing glaciers. The timing of when the glacier killed the moss provides an archive of glacier history. For example, when glaciers expand or advance, they can entomb or cover the plant—starving it of light and warmth. The date the plant died is the same time the glacier advanced over that location. As glaciers recede, these previously entombed mosses are exposed and are dead and black. “What’s so valuable about these kill dates compared to other records (like the ages of glacial erratics or penguin remains) is their accuracy,” says Groff. They provide a clearer picture of the climate history owing to their direct carbon exchange with the atmosphere and decreased error around the age estimate.

Groff and colleagues collected black mosses around the northern Antarctic Peninsula by exploring the edges of glaciers and nunataks at several locations. By radiocarbon dating the mosses, they found that glaciers advanced three times in the past 1,500 years. This is evidence for phases of cooler and potentially wetter conditions than today. On Anvers Island, they learned that the last time the glacier was at its 2019 position was around 850 years ago as it expanded over the course of several centuries. Their estimates of glacier advance are much slower than recent retreat. “Interestingly, we found that the glacier front with the fastest advance also had the fastest retreat, suggesting that hotspots of rapid coastal glacier dynamics occur in the Antarctic Peninsula, says Groff.

This is a unique dataset because it’s rare to have past net advance rates in the literature because glacial records tend to be destroyed when the glacier advances. These black mosses can reliably be used to estimate glacier advances in the past. “There are other lines of evidence that support our moss kill dates for past cooler conditions, such as peat records indicating lower biological productivity, as well as evidence for sea-level change from raised beaches as a result of changing ice mass. It’s also possible that the climate conditions that led to glacier advances involved wetter conditions and would have had a negative impact on penguins, as we know they do today. Many of the recent abandoned penguin colonies are the same age as our youngest black moss,” says Groff.

FEATURED ARTICLE

Kill dates from re-exposed black mosses constrain past glacier advances in the northern Antarctic Peninsula
Dulcinea V. Groff; David W. Beilman; Zicheng Yu; Derek Ford; Zhengyu Xia
Contact: Dulcinea V. Groff, dulcineavgroff@gmail.com, Department of Geology & Geophysics, University of Wyoming, Laramie, Wyoming 82073, USA; Department of Earth & Environmental Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA
 

GEOLOGY articles are online at https://geology.geoscienceworld.org/content/early/recent . Representatives of the media may obtain complimentary articles by contacting Kea Giles at the e-mail address above. Please discuss articles of interest with the authors before publishing stories on their work, and please make reference to GEOLOGY in articles published. Non-media requests for articles may be directed to GSA Sales and Service, gsaservice@geosociety.org.

https://www.geosociety.org

Cape Rasmussen, one of the study sites mentioned in the paper. Credit: Derek J. Ford.

CREDIT   Derek J. Ford

Drone Video of Cape Rasmussen [VIDEO] | EurekAlert! Science News Releases

JOURNAL

Geology

DOI

10.1130/G50314.1 

ARTICLE TITLE

Kill dates from re-exposed black mosses constrain past glacier advances in the northern Antarctic Peninsula

New study suggests that when forecasting trends, reading a bar chart versus a line graph biases our judgement.

Study suggests that judgmental forecasting by non-experts of trends in time-series data, such as weekly sales data, is consistently lower when the information is displayed in bar chart format as opposed to a line graph or point graph.

Peer-Reviewed Publication

CITY UNIVERSITY LONDO

A new study suggests that the format in which graphs are presented may be biasing people into being too optimistic or pessimistic about the trends the graphs display.

Academics from City, University of London and University College London found that when people made predictions about how a trend would develop over time, they made lower judgements when the trend was presented as a ‘bar chart’ type graph than when exactly the same data was presented as a line graph or a graph consisting of a set of data points only.

The study comprised four experiments conducted online with over four thousand participants in total.  In the first two experiments, participants were each given a single graph, either a bar chart, line graph or point graph, populated with 50 datapoints representing weekly sales made by a fictitious company. Participants had to click on the graph to show how many sales they thought the company would make in the eight weeks that followed. They were incentivised to give accurate responses.

In the first experiment the number of sales in the graph provided increased week on week, and participants generally forecast that sales would increase further; in the second experiment, the trends in the graph were decreasing making participants more pessimistic about sales in the future.

Nevertheless, across many different types of trend participants consistently thought sales would be lower when the data were presented as bar charts than line graphs or point graphs.

The researchers wondered whether the reason was that in bar charts the area inside the bar is usually heavily shaded and hence visually draws attention to itself, lowering participants’ estimates as compared to the other types of graph where there is no shading to attract the eye and attention. However, in a third experiment, they found the same lower forecasts for bars even when the bars were left unshaded.

In a fourth experiment they tested a version of a bar chart where the bars emanated from the top of the graph rather than the bottom. While subtle trends in the data suggest this may reverse the bias, the findings were inconclusive.

Stian Reimers, Professor of Psychology and Behavioural Science at the School of Health & Psychological Sciences, City, University of London, and who led the research said:

“In the past few years it seems like we have spent a lot of time looking at time series: whether it’s the number of Covid cases, electricity prices or inflation rates, to try to work out what’s coming next. What our research shows is that our predictions of what we think will happen next are affected not just by the trends we’re looking at, but the format in which they’re displayed. This obviously has implications for all of us as we try to make decisions on whether it’s likely to be safe to visit vulnerable relatives, or whether we’ll be able to afford to take on a mortgage.”

As well as affecting the decisions that individuals make, these biases may also affect the many businesses that perform analyses like ‘demand forecasting,’ where historical data is used to estimate and predict customers' future demand for a product or service; specifically when these judgements are made unaided by individuals directly ‘eyeballing’ graphs and estimating how they think a trend is going to develop.

However, Professor Reimers believes these biases could have benefits:

“It’s potentially useful because these kinds of format effect might help counteract some of the other errors people make when projecting trends into the future. A lot of the other biases that people show when trying to extrapolate trends are baked into the way we see the world and hard to change. The format we use for our graphs is something we have complete control over, so it may be possible to use specific formats to help undo people’s built-in biases and help people make more accurate judgements.

“Although we had a lot of participants, this is just a small set of studies. It will be interesting to see how well these findings generalise across different formats and levels of expertise, and exciting to try to find the ways of presenting data that unfolds over time in a way that helps people best capture the state of the world and most accurately predict what is likely to happen next.”

The research is published open access in the International Journal of Forecasting.

ENDS

Notes to editors

Contact details:

To speak to Professor Stian Reimers, contact Dr Shamim Quadir, Senior Communications Officer, School of Health & Psychological Sciences. Tel: +44(0) 207 040 8782 Email: shamim.quadir@city.ac.uk.

Read the full study in the International Journal of Forecasting

Bars, lines and points: The effect of graph format on judgmental forecasting

https://www.sciencedirect.com/science/article/pii/S0169207022001467?via%3Dihub

Graphs for illustrative purposes only*

Example illustration of the three types of graph used in the study can be downloaded from the journal website here: a bar chart (left), point graph(centre) and line graph (right).  *Please note this is an illustrative example, and the graphs here do not show the same data as each other.

About City, University of London

City, University of London is a global higher education institution committed to academic excellence, with a focus on business and the professions and an enviable central London location.

City’s academic range is broadly-based with world-leading strengths in business; law; health sciences; mathematics; computer science; engineering; social sciences; and the arts including journalism and music.

City has around 20,000 students (46% at postgraduate level) from more than 160 countries and staff from over 75 countries.

In the last REF, City doubled the proportion of its total academic staff producing world-leading or internationally excellent research.

More than 140,000 former students from over 180 countries are members of the City Alumni Network.

The University’s history dates from 1894, with the foundation of the Northampton Institute on what is now the main part of City’s campus.  In 1966, City was granted University status by Royal Charter and the Lord Mayor of London became its Chancellor. In September 2016, City joined the University of London and HRH the Princess Royal became City’s Chancellor.

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JOURNAL

International Journal of Forecasting

DOI

10.1016/j.ijforecast.2022.11.003 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Bars, lines and points: The effect of graph format on judgmental forecasting.

How salmon feed flowers & flourishing ecosystems: Study

Peer-Reviewed Publication

SIMON FRASER UNIVERSITY

 

IMAGE: RESEARCHERS FOUND THAT THE ADDITION OF SALMON CARCASSES LED TO LARGER LEAVES, PARTICULARLY IN YARROW AND COMMON RED PAINTBRUSH, AND A GREATER SEED SET IN YARROW IN THE THIRD YEAR. view more 

CREDIT: ALLISON DENNERT, SIMON FRASER UNIVERSITY

Nutrients from salmon carcasses can substantively alter the growth and reproduction of plant species in the surrounding habitat, and even cause some flowers to grow bigger and more plentiful, SFU researchers have found.

Their study, published today in the journal Royal Society Open Science, is the first to demonstrate a connection between salmon and coastal plant growth and reproduction. The work extends what has previously been known about a nitrogen isotope that is found in some plants and animals in the ecosystem and has been generally attributed to the nutrients from salmon.

It also sheds light on the bigger picture of how the impact of climate change on the rivers and streams travelled by salmon could help to inform ecosystem planning and management.

During a three-year field study, researchers experimentally added pink salmon carcasses into the estuary of a small river in Haíɫzaqv (Heiltsuk) territory on B.C.’s central coast. The area features a large meadow of grasses and wildflowers.

“Following our experiments, we found that some species of wildflower grew larger leaves where a salmon carcass was deposited, and in some years, some species grew larger flowers or produced more seeds,” says PhD biology student Allison Dennert, who led the research, working with SFU biology professors Elizabeth Elle and John Reynolds.

The team undertook similar experiments using drift seaweed rockweed, which provides a different set of nutrients. They also experimented with a combination of rockweed and salmon carcasses, and a control, then examined their impacts on four common wildflower species, including silverweed, yarrow, Douglas’ aster and common red paintbrush.

Researchers found that the addition of salmon carcasses led to larger leaves, particularly in yarrow and common red paintbrush, and a greater seed set in yarrow in the third year.

"Understanding the interconnection between ecosystems is incredibly important to our knowledge of how to protect them,” says Dennert, who also works with the Raincoast Conservation Foundation.

“Currently, lands and waters are managed under separate provincial and federal jurisdictions. Scientifically and management-wise, we think of the land and sea as separate and unconnected entities. This work furthers the idea that ecosystems don’t exist in isolation, and that what happens in one can influence the other.”

The research comes as salmon in the region continue to see declines. Research published last summer by SFU alumnus Will Atlas found that chum salmon abundance in the team’s study region declined almost 50 per cent within the last 15 years, and over 70 per cent within the last 50 years.

Dennert was among researchers who found thousands of decaying salmon in a dried up river in the Heiltsuk Nation last summer. “In some areas on our coast,” she notes, “we’re rapidly losing salmon biomass and the ocean’s connection to life on land."

Research lead, PhD biology student Allison Dennert with SFU biology's Reynolds Lab and the Earth2Ocean Research Group.

Research lead, PhD biology student Allison Dennert with SFU biology's Reynolds Lab and the Earth2Ocean Research Group.

CREDIT

Simon Fraser University

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JOURNAL

Royal Society Open Science

DOI

10.1098/rsos.221008 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Experimental addition of marine-derived nutrients affects wildflower traits in a coastal meta-ecosystem

ARTICLE PUBLICATION DATE

25-Jan-2023

80-year-old medical mystery that caused baby deaths solved

Peer-Reviewed Publication

UNIVERSITY OF EAST ANGLIA

Researchers at the University of East Anglia have solved an 80-year-old medical mystery that causes kidney damage in children and can be fatal in babies.

Those affected by the condition cannot metabolise vitamin D properly, causing a build-up of calcium in the blood and leading to kidney damage and kidney stones.

It led to a wave of baby deaths in the 1930s and 1940s, after foods such as milk, bread, cereal, and margarine were fortified with Vitamin D in a bid to eradicate rickets in children.

Recent research had shown that the condition, now known as infantile hypercalcaemia type 1, is caused by a gene mutation. But curiously, around 10 per cent of patients experiencing symptoms do not have the genetic mutation.

“This really puzzled us,” said lead researcher Dr Darrell Green, from UEA’s Norwich Medical School. “So we wanted to find out exactly why this 10 per cent appeared to have the condition, but without the gene mutation that was found to cause it.”

The puzzle began in the early 1900s, when more than 80 per cent of children in industrialised Europe and North America were affected by rickets, which causes bone pain, poor growth and soft, weak, deformed bones.

The discovery that sunlight prevented rickets led to fortification of foods with vitamin D, which all but eradicated the disease by the 1930s. But outbreaks of vitamin D intoxication in infants led to fortification bans in many European countries by the 1950s.

Dr Green said: “Foods such as dairy products had been fortified with vitamin D, but it led to a number of baby deaths, and was eventually banned in many countries except for in breakfast cereals and margarine.

“In 2011, researchers found that some people are born with a mutation in the CYP24A1 gene, which means they cannot metabolise vitamin D properly. This causes a build-up of calcium in the blood, leading to kidney stones and kidney damage, which can be fatal in babies. It was the reason why vitamin D-fortified food in the 1930s caused intoxication in some people.

“Today, some people do not realise they have a CYP24A1 mutation until they are adults, after years of recurrent kidney stones and other problems. In most cases, these patients are screened and find out that they have the CYP24A1 mutation and the disorder now known as infantile hypercalcemia type 1, or HCINF1.

“However, in around 10 per cent of suspected HCINF1 patients, they do not display an obvious mutation in CYP24A1 and continue to have lifelong problems without a proper diagnosis.”

The UEA team collaborated with colleagues at the Norfolk and Norwich University Hospital, where they worked with 47 patients.

They used a combination of next generation genetic sequencing and computational modelling to study blood samples from those ’10 per cent’ of puzzling patients.

Dr Green said: “A PhD student in my laboratory, Nicole Ball, carried out a more extensive genetic analysis of six patient blood samples and we found that the physical shape of the CYP24A1 gene in these apparent HCINF1 patients is abnormal.

“This tells us that gene shape is important in gene regulation - and that this is the reason why some people lived with HCINF1 but without a definitive diagnosis”, he added.

“On a wider scale relevant to genetics and health, we know that genes must have the correct sequence to produce the correct protein, but in an added layer of complexity, we now know that genes also have to have a correct physical shape,” added Dr Green.

Prof Bill Fraser, from both Norwich Medical School and the Norfolk and Norwich University Hospital, co-led the study and treats HCINF1 patients in metabolic bone clinics.

He said: “Genetic causes of vitamin D toxicity can be left undiagnosed for long periods, well into adulthood, sometimes coming to light during pregnancy when fortification of mothers with vitamin D happens. We also see patients with undiagnosed causes of recurrent renal stones who have had this condition for many years.

“Treatment includes avoidance of vitamin D supplementation in subjects with the particular genetic abnormalities we have identified.

“A beneficial side effect to some anti-fungal medications includes alteration of vitamin D metabolism lowering active vitamin D, which decreases calcium levels and can give patients a more normal quality of life, which we have started to prescribe in some patients,” he added.

The researchers now plan to investigate the role of gene shapes in other disorders such as cancer.

This research was led by UEA in collaboration with the John Innes Centre, the Norfolk and Norwich University Hospital, Croydon University Hospital, and the Royal Hospital for Children in Glasgow.

‘3’ untranslated region structural elements in CYP24A1 are associated with Infantile hypercalcaemia type 1’ is published in the Journal of Bone and Mineral Research,

CASE STUDY – Shelley O’Connor

Shelley O’Connor, 34, from Norwich, was diagnosed with infantile hypercalcaemia type 1 eleven years ago when she fell pregnant with her first child at the age of 23.

She had started to take pregnancy supplements, which included vitamin D. But she began to experience a pain so severe that midwives thought she was going into an early labour at just 23 weeks.

“It was very frightening,” she said. “I was in a lot of pain, and the midwives thought I was going into labour. I was really scared for the baby, but when I had an MRI, they found out that it was actually a kidney stone caused by taking vitamin D as a pregnancy supplement.”

Thankfully, her son was born safe and well at full term, and Shelley has since gone on to have another two children.

“I was diagnosed with HCINF1 and it did explain a lot because I had experienced things like abdominal pain and UTIs in childhood,” she said. 

But the condition has taken its toll. Shelley now regularly passes kidney stones and needs to take pain medication. She also has to have an operation every six months to clear the calcium build-ups that lead to kidney stones.

“I was really pleased to be invited to take part in the research, and I hope the findings go on to help others like me,” she said.

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JOURNAL

Journal of Bone and Mineral Research

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

3’ untranslated region structural elements in CYP24A1 are associated with Infantile hypercalcaemia type 1

ARTICLE PUBLICATION DATE

26-Jan-2023