Decades of nuclear energy research pay off in milestone nonproliferation achievement

Argonne scientists help facilities around the world convert to safer processes and materials without halting production of lifesaving medical radioisotopes

Grant and Award Announcement

DOE/ARGONNE NATIONAL LABORATORY

 

IMAGE: AERIAL VIEW OF ARGONNE NATIONAL LABORATORY. view more 

CREDIT: (IMAGE BY ARGONNE.)

When the U.S. Department of Energy’s (DOE) National Nuclear Security Administration (NNSA) announced that it had reached a major nonproliferation milestone this week, many at Argonne National Laboratory, a DOE national laboratory, felt a surge of pride.

Scientists and engineers at Argonne have been working for decades to help medical isotope production facilities around the world change from the use of highly enriched uranium (HEU) to the use of low-enriched uranium (LEU), which is much more difficult to use in a weapon. The successful conversion of Belgium’s National Institute of Radioelements (IRE) was the last step in completion of the effort.

“Our scientists and engineers work diligently to see problems solved and challenges overcome, and this is a moment when we can celebrate the impact of that diligence worldwide.” — Temitope Taiwo, director of Nuclear Science and Engineering, Argonne

“As a result of this accomplishment, all major global molybdenum-99 production facilities now use LEU,” said Temitope Taiwo, director of the Nuclear Science and Engineering division at Argonne. ​“Our scientists and engineers work diligently to see problems solved and challenges overcome, and this is a moment when we can celebrate the impact of that diligence worldwide.”

Molybdenum-99’s (Mo-99) decay product, technetium-99m (Tc-99m), is used in over 40,000 medical procedures in the United States each day, including for the diagnosis of heart disease and cancer. Historically, Mo-99 was usually produced by irradiating HEU in nuclear reactors and then processing the irradiated material to extract the Mo-99. The uranium placed in the reactor for irradiation is known as a ​“target.” HEU is a proliferation-sensitive material that, if diverted or stolen, could be used as a component of a nuclear weapon.

“Thanks to the hard work of the NNSA team and our partners, including Belgium’s IRE, all major Mo-99 producers can now perform their vital work without the use of proliferation-sensitive HEU targets,” said NNSA Administrator Jill Hruby. ​“This also means that all of the Mo-99 used in the United States is now produced without highly enriched uranium targets.”

Fulfilling a commitment made at the 2012 Nuclear Security Summit, NNSA provided financial and technical assistance to global Mo-99 producers for the conversion from HEU to LEU targets. Argonne helped with these technically complex conversions, which included requiring qualification of new LEU targets for irradiation in nuclear reactors, modification of specialized equipment for processing irradiated targets, and extensive reviews from both nuclear safety and medical regulators.

“It was good chemistry — not only re-evaluating the uranium processes from the ground up but also the chemistry between the IRE and DOE staff — that led to the successful conversion and manufacturing of this life-saving isotope,” said M. Alex Brown, a nuclear chemical engineer in Argonne’s Chemical and Fuel Cycle Technologies division.

The progress made in converting global Mo-99 producers to LEU enabled the U.S. secretaries of Energy and Health and Human Services to jointly certify in December 2021 that there is a sufficient global supply of Mo-99 produced without the use of HEU to meet the needs of U.S. patients. This certification triggered a ban on U.S. exports of HEU for foreign medical isotope production.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.

The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://​ener​gy​.gov/​s​c​ience.

‘Green’ way to extract hair compounds that could be used for bandages, sunscreens

AMERICAN CHEMICAL SOCIETY

Hair styling can be a potent form of self-expression, whether it features dramatic updos, intricate braids or crazy colors. Beyond being a reflection of our personality, these strands contain compounds that could one day appear in bandages, sunscreens or other products. Researchers reporting in ACS Omega have now designed a simple, green process to extract both keratin and melanin from human hair for these possible applications without harsh chemicals or excessive waste.

Hair is made up of protein filaments consisting of many different layers and components. Its structure comes from the protein keratin, which can also be found in fingernails, horns and feathers. Its color is provided by melanin, a group of pigment molecules that are also found in the skin and eyes. In addition, melanin has antioxidative properties and can help shield against ultraviolet light. These qualities make the compounds suitable for biomedical applications; however, since most discarded hair is incinerated or dumped in landfills, its keratin and melanin are largely unused as well. Chemically extracting them from hair is possible, but current protocols either can only extract one compound at a time, or rely on harsh chemicals and complicated steps. So, Paulomi Ghosh and colleagues wanted to develop a straightforward method to extract both keratin and melanin from human hair with a single procedure, using a recyclable, green solvent.

The researchers collected samples of hair from local salons, then washed and cut them into small slices. Then, they mixed the hair with an ionic liquid, which dissolved the mixture by interrupting the hydrogen bonds that held the keratin proteins together. When heated and poured into a hydrochloric acid solution, the melanin pigments precipitated out and were collected. Next, the researchers performed dialysis to collect the keratin proteins. The ionic liquid was recycled and reused in subsequent reactions, without a significant impact on the reaction’s yield.

Recovered keratin was compatible with blood, suggesting that it could be used in heavy-duty hemostatic bandages. This extraction procedure also maintained the natural structure of the melanin, which was lost in other, harsher methods. Because the melanin had good antioxidative and UV shielding properties, the team says it could be used in sun-protective products or films. The researchers say that this technique could serve as a green way to sustainably extract useful biopolymers from otherwise discarded materials.

The authors acknowledge funding from the Department of Science and Technology (DST)-INSPIRE Faculty, the CSIR-Indian Institute of Chemical Biology, the Indian Council of Medical Research and the Department of Biotechnology of the Government of India.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

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JOURNAL

ACS Omega

DOI

10.1021/acsomega.3c01428 

ARTICLE TITLE

“One-Pot Extraction of Bioresources from Human Hair via a ZeroWaste Green Route”

Mental imagery a helpful way to distract teens from negative thought patterns, OSU study finds

OREGON STATE UNIVERSITY

For adolescents who may get stuck in negative thought spirals, refocusing on mental imagery is a more effective distraction than verbal thoughts, a recent study from Oregon State University found.

A short-term distraction can break up the thought spiral, which makes room for that person to then seek help from a therapist, friend or parent, said study author Hannah Lawrence, an assistant professor of psychology in OSU’s College of Liberal Arts.

“When we get stuck thinking about negative things that happened in the past, that makes us feel even worse, and it leads to more difficulties regulating our emotions and regulating our bodies,” Lawrence said. “We want to connect people to some more comprehensive strategies or skills that could get us unstuck from those thinking patterns.”

Lawrence runs the Translational Imagery, Depression and Suicide (TIDES) Lab at OSU, researching risk factors and developing effective interventions for depression in adolescents, including interventions that can be scaled up so they’re accessible to a wider population.

“These negative things are going to happen to all of us, so knowing ahead of time which tools we should pack in our toolbox that we can pull out to help lower our emotional reactions in the moment, just enough to get us out of those loops, will help us get unstuck,” she said.

The study, published in the Journal of Affective Disorders, aimed to determine which form of negative rumination — either verbal thoughts or imagery-based thoughts — caused a greater drop in the adolescent participants’ affect, or general mood; and also which form of thought was more effective at distracting them and helping them break out of that negative mood.

The 145 participants were ages 13 to 17 and recruited from a rural area of New England where Lawrence conducted the research study. The group was predominantly white and 62% female. Participants also filled out a depression questionnaire, which showed that about 39% of the group experienced clinically elevated symptoms of depression.

The researchers started by inducing a negative mood in the teenage participants, using an online game designed to create feelings of exclusion. (After participants completed the study, researchers explained the game to them to help alleviate any lingering hurt feelings.)

Participants were then split into groups and prompted to ruminate, either in verbal thoughts or mental imagery; or prompted to distract themselves, also in verbal thoughts or mental imagery. In the rumination group, participants were given prompts like “Imagine the kind of person you think you should be.” In the distraction group, prompts such as “Think about your grocery list” were meant to distract them from their negative affect.

To encourage verbal thoughts, researchers had participants practice coming up with sentences in their head describing a lemon using specific words. To encourage mental imagery, they had participants practice imagining what a lemon looked like in different conditions.

Researchers used noninvasive sensors to record electrical activity of the heart and skin conductance response as a way to measure physiological responses to the various prompts. They also directed participants to rate their current emotional affect at four different points during the study.

While there was no significant difference in the adolescents’ response between the two types of rumination — both verbal thoughts and mental imagery had a similar effect on their mood — researchers found that mental imagery was significantly more effective as a distraction than verbal thoughts.

“Using mental imagery seems to help us improve our affect, as well as regulate our nervous system,” Lawrence said. “The fact that we didn’t have a significant result for ruminating in imagery versus verbal thought tells us that it doesn’t really matter what form those negative cognitions take. The part that seems really problematic is the getting-stuck part — dwelling over and over again on these sad or anxiety-inducing things that happen.”

Researchers don’t know exactly why mental imagery is so effective, but they hypothesize it’s because imagery is much more immersive and requires more effort, thus creating a stronger emotional response and a bigger distraction. There’s also some evidence that imagining mental pictures lights up the same part of the brain as seeing and experiencing those things in real life, Lawrence said. 

In her work, Lawrence has found some adults seem to ruminate in only one form, while most teens report ruminating in both verbal thoughts and mental imagery. One possibility is that these thought patterns become self-reinforcing habits, she said, with the negative images or verbal messages becoming more ingrained over time.

“That’s why I like working with teenagers: If we can interrupt these processes early in development, maybe we can help these teens get to adulthood and not get stuck in these negative thinking patterns,” Lawrence said. “All of us ruminate. It’s a matter of how long we do it for, and what skills we have to stop when we want to.”

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JOURNAL

Journal of Affective Disorders

DOI

10.1016/j.jad.2023.02.066 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Reimagining rumination? The unique role of mental imagery in adolescents' affective and physiological response to rumination and distraction

Climate change could drive more Zika and dengue epidemics and longer transmission seasons in Brazil, with a new model predicting Zika's R0 increasing up to 2.7

PLOS

Climate change could drive more Zika and dengue epidemics and longer transmission seasons in Brazil, with a new model predicting Zika's R0 increasing up to 2.7.

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Article URL: http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010839

Article Title: Long-term projections of the impacts of warming temperatures on Zika and dengue risk in four Brazilian cities using a temperature-dependent basic reproduction number

Author Countries: USA

Funding: This work was supported in part by a grant from the National Institutes of Health (www.nih.gov; grant number R01AI132372). HVW and JNSE received funding from this source. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

JOURNAL

PLoS Neglected Tropical Diseases

DOI

10.1371/journal.pntd.0010839 

ARTICLE TITLE

Long-term projections of the impacts of warming temperatures on Zika and dengue risk in four Brazilian cities using a temperature-dependent basic reproduction number

ARTICLE PUBLICATION DATE

27-Apr-2023

Modern-day Scottish, Welsh and Northern Irish people have Pictish ancestry

PLOS

The Picts of Scotland who have long intrigued and have been ascribed exotic origins in fact descended from indigenous Iron Age society and were genetically most similar to people living today in Scotland, Wales, North Ireland and Northumbria. Adeline Morez of Liverpool John Moores University and Linus Girdland-Flink of the University of Aberdeen report these findings in a new study published April 27 in the journal PLOS Genetics.

The Picts, who inhabited early medieval Scotland from about 300-900 AD, formed the first documented kingdoms of eastern Scotland, but have often been a subject of mystery due to the lack of historical and archaeological evidence and due to their enigmatic symbol tradition inscribed on stone. In their new study, Morez and Girdland-Flink sampled Pictish burials to extract genomes to explore how the Picts are related to other cultural groups in Britain. They sequenced DNA from two individuals from central and northern Scotland that dated from the fifth to the seventh century AD. They compared the resulting high-quality genomes to more than 8,300 previously published ancient and modern genomes.

The analysis revealed that Picts descended from local Iron Age populations, who lived across Britain before the arrival of mainland Europeans. Additionally, the researchers found genetic similarities between the Picts and present-day people living in western Scotland, Wales, Northern Ireland and Northumbria. Medieval traditions, including from the time of the Picts themselves, had ascribed exotic origins to the Picts including them coming from Thrace (north of the Aegean Sea), Scythia (eastern Europe), or isles north of Britain, but the new research suggests much less sensational origins.

A further analysis of DNA sequenced from seven individuals interred in a Pictish cemetary showed that the individuals did not share a common ancestor on their mother’s side. This finding suggests that females may have married outside their own social group and runs counter to older speculation, such as that mentioned by the great English scholar Bede, that the Picts were matrilineal; that they had had a society based on kinship through the mother’s lineage.

The new findings support current archaeological theories that Picts descended from Iron Age people in Britain. The study also provides novel insights into the genetic relationships that existed amongst Pictish individuals buried in cemeteries together and between ancient Picts and present-day groups in the United Kingdom.

####

Author Interview:

PLOS: What first drew you to study paleogenetics?

Dr. Morez: I always have been fascinated by human evolution overall: where are we from? How did we manage to settle worldwide and adapt to the wide diversity of environments? I chose to focus on paleogenetics, the study of ancient DNA, as it is a formidable opportunity to gain direct knowledge of an individual ancestry or a population's genetic diversity, free from inference based on modern genomes. And now, we actually see that the migrations and population mixtures are more numerous and complex than previously hypothesised.

PLOS:  What did you choose to investigate in this study, and why?

Dr. Morez: In this study, I chose to investigate the genetic ancestry of the Picts - people living in Scotland during the early medieval period (here from individuals buried in eastern and northern Scotland). It has never been done and many historical-based hypotheses stated that they were biologically diverse from their neighbours, with possible ties from the Eurasian steppes. Once we realised they were actually genetically very similar to their contemporaries living in the UK, we decided to push the limit in terms of analytical resolution using imputation of genotypes and analyses based on the autosomal haplotype information (chunks of DNA shared from parents to offspring, modify by mutation and recombination). It allows us to study the fine-scale genetic structure between the Picts and ancient and modern individuals from the UK and Europe.

PLOS: What are the key findings from your research on ancient Pictish genetics?

Dr. Morez: The two Picts studied here showed a greater affinity (by haplotype sharing) with present-day populations from western Scotland, Wales, Northern Ireland and Northumbria compared to the populations from southern England, which is important for understanding how present-day diversity formed in the UK.

Thanks to comparison with previously published genomes from Pictish people living in the Orkney islands, we could also show that individuals living in the Orkney and in mainland Scotland, likely gathered under the same cultural unit, were slightly divergent likely because of limited gene flow between the two regions and small population size in Orkney, which is known to speed up genetic divergence.

PLOS: What most surprised or interested you about your findings?

Dr. Morez: I was surprised to find that the two Pictish genomes from eastern and northern Scotland show a slightly higher but noticeable haplotype sharing with present-day people living in western Scotland, rather than with those from the East where Pictish culture is believed to thrive. This was unexpected and may be caused by several reasons; either we are detecting a population movement from the west of Scotland toward the east but which did not leave a long-lasting genetic signature, or later population movements in the East replaced some of the Pictish ancestry. We still don’t know which one is correct.

PLOS: What do you hope your findings might lead to, and what are the next steps for your research?

Dr. Morez: I hope the fascination for the Iron Age and medieval period in the UK will increase and lead to more genomes being discovered and analysed, to get a better understanding of the genetic structure across Scotland. Thanks to these genomes, those already published and the many more yet to come, the UK will soon become the first country where we understand in detail how genetic diversity has formed.

Future research will provide new information on the Pictish lifestyle, thanks to archaeologists from the University of Aberdeen and co-authors of the study. Gordon Noble who is reassessing and excavating new Pictish sites, and Kate Britton who investigates dietary habits and mobility using stable isotopes. Linus Girdland Flink (senior author, University of Aberdeen) is coordinating further research on Pictish DNA. This ongoing project will provide an excellent tool to facilitate interdisciplinary research to connect archaeology, archaeological science, history, and human population genetics.

 

#####

In your coverage, please use this URL to provide access to the freely available article in PLOS Genetics:

http://journals.plos.org/plosgenetics/article?id=10.1371/journal. pgen.1010360

Citation: Morez A, Britton K, Noble G, Günther T, Götherström A, Rodríguez-Varela R, et al. (2023) Imputed genomes and haplotype-based analyses of the Picts of early medieval Scotland reveal fine-scale relatedness between Iron Age, early medieval and the modern people of the UK. PLoS Genet 19(4): e1010360. https://doi.org/10.1371/journal.pgen.1010360

Author Countries: Germany, Sweden, UK

Funding: AM was supported by ECR strategic support of early career researchers in the faculty of science at LJMU, awarded to LGF. LGF was supported by the School of Geoscience, University of Aberdeen. KB was supported by the Leverhulme Trust (PLP-2019-284) during production of this manuscript. 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 Genetics

DOI

10.1371/journal.pgen.1010360 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE PUBLICATION DATE

27-Apr-2023

Robert Louis Stevenson

Heather Ale

A GALLOWAY LEGEND

From the bonny bells of heather
  They brewed a drink long-syne,
Was sweeter far then honey,
  Was stronger far than wine.
They brewed it and they drank it,
  And lay in a blessed swound
For days and days together
  In their dwellings underground.

There rose a king in Scotland,
  A fell man to his foes,
He smote the Picts in battle,
  He hunted them like roes.
Over miles of the red mountain
  He hunted as they fled,
And strewed the dwarfish bodies
  Of the dying and the dead.

Summer came in the country,
  Red was the heather bell;
But the manner of the brewing
  Was none alive to tell.
In graves that were like children's
  On many a mountain head,
The Brewsters of the Heather
  Lay numbered with the dead.

The king in the red moorland
  Rode on a summer's day;
And the bees hummed, and the curlews
  Cried beside the way.
The king rode, and was angry,
  Black was his brow and pale,
To rule in a land of heather
  And lack the Heather Ale.

It fortuned that his vassals,
  Riding free on the heath,
Came on a stone that was fallen
  And vermin hid beneath.
Rudely plucked from their hiding,
  Never a word they spoke;
A son and his aged father --
  Last of the dwarfish folk.

The king sat high on his charger,
  He looked on the little men;
And the dwarfish and swarthy couple
  Looked at the king again.
Down by the shore he had them;
  And there on the giddy brink --
"I will give you life, ye vermin,
  For the secret of the drink."

There stood the son and father,
  And they looked high and low;
The heather was red around them,
  The sea rumbled below.
And up and spoke the father,
  Shrill was his voice to hear:
"I have a word in private,
  A word for the royal ear.

"Life is dear to the aged,
  And honour a little thing;
I would gladly sell the secret,"
  Quoth the Pict to the king.
His voice was small as a sparrow's,
  And shrill and wonderful clear:
"I would gladly sell my secret,
  Only my son I fear.

"For life is a little matter,
  And death is nought to the young;
And I dare not sell my honour
  Under the eye of my son.
Take him, O king, and bind him,
  And cast him far in the deep;
And it's I will tell the secret
  That I have sworn to keep."

They took the son and bound him,
  Neck and heels in a thong,
And a lad took him and swung him,
  And flung him far and strong,
And the sea swallowed his body,
  Like that of a child of ten; --
And there on the cliff stood the father,
  Last of the dwarfish men.

"True was the word I told you:
  Only my son I feared;
For I doubt the sapling courage
  That goes without the beard.
But now in vain is the torture,
  Fire shall never avail:
Here dies in my bosom
  The secret of Heather Ale."

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NOTE TO HEATHER ALE

Among the curiosities of human nature this legend claims a high place. It is needless to remind the reader that the Picts were never exterminated, and form to this day a large proportion of the folk of Scotland, occupying the eastern and the central parts, from the Firth of Forth, or perhaps the Lammermoors, upon the south, to the Ord of Caithness on the north. That the blundering guess of a dull chronicler should have inspired men with imaginary loathing for their own ancestors is already strange; that it should have begotten this wild legend seems incredible. Is it possible the chronicler's error was merely nominal? that what he told, and what the people proved themselves so ready to receive, about the Picts, was true or partly true of some anterior and perhaps Lappish savages, small of stature, black of hue, dwelling underground -- possibly also the distillers of some forgotten spirit? See Mr. Campbell's Tales of the West Highlands.

Novel biomarker score could help measure adherence to Mediterranean diet

New evidence suggests Mediterranean diet may reduce type 2 diabetes risk more than previously thought

Peer-Reviewed Publication

PLOS

 

IMAGE: RESEARCHERS DEVELOPED A NEW WAY TO DETECT WHETHER SOMEONE FOLLOWS A MEDITERRANEAN DIET USING A BLOOD TEST AND SHOWED THAT A MEDITERRANEAN DIET IS ASSOCIATED WITH LOWER RISK OF TYPE 2 DIABETES. view more 

CREDIT: GALYAFANASEVA, PIXABAY (CC0, HTTPS://CREATIVECOMMONS.ORG/PUBLICDOMAIN/ZERO/1.0/)

Researchers have developed a novel way to detect whether a person follows a Mediterranean diet using a blood test and, applying this method, have shown that a Mediterranean diet is associated with lower risk of type 2 diabetes. Jakub Sobiecki of the University of Cambridge, UK and colleagues present these findings April 27th in the open access journal PLOS Medicine.

Prior research has shown that people who self-report that they follow a Mediterranean diet have a modestly lower risk of type 2 diabetes. However, the subjectivity of self-reports makes that link uncertain. Until now, the potential link between a Mediterranean diet and type 2 diabetes risk has not been evaluated using objective biological indicators—biomarkers—of adherence to the diet.

Sobiecki and colleagues developed a novel biomarker-based indicator of a Mediterranean diet that incorporates levels of certain molecules in the blood. First, the researchers identified that blood levels of 24 fatty acids and 5 carotenoids could be applied to predict whether participants from a clinical trial of 128 people were assigned to following a Mediterranean diet. Levels of these molecules in a person’s blood were used to calculate a biomarker score, which the researchers used as a measure of the extent to which they followed a Mediterranean diet.

Next, the researchers applied the biomarker score in a study of 340,234 people living in eight European countries, of whom 9,453 developed type 2 diabetes during follow-up and had relevant biomarkers measured. Comparing them with 12,749 participants who remained free of type 2 diabetes, the researchers found that people whose biomarker score indicated greater adherence to a Mediterranean diet were less likely to develop type 2 diabetes.

For comparison, the researchers also asked participants to self-report their diet. They found that using the biomarker score identified a stronger link between the Mediterranean diet and reduced risk of type 2 diabetes than when self-report was used. This finding suggests that previous self-report-based studies may have underestimated the association.

Based on these findings, the researchers argue that even a modest improvement in people’s adherence to a Mediterranean diet could meaningfully reduce the incidence of type 2 diabetes. However, they also point out that additional research will be needed to confirm and extend these new findings since it is currently unknown to what extent the biomarker score is specific for the Mediterranean diet.

Senior author Professor Nita Forouhi said, “Our research combining information from a dietary clinical trial and a large cohort study to identify and apply blood biomarkers for a dietary pattern is exciting and should stimulate development of improved methods to study diet-disease associations which are typically limited by reliance on subjective recall of eating.”

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In your coverage, please use this URL to provide access to the freely available paper in PLOS Medicine: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004221

Citation: Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, et al. (2023) A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study. PLoS Med 20(4): e1004221. https://doi.org/10.1371/journal.pmed.1004221

Author Countries: United Kingdom, Australia, Spain, Germany, China, Italy, Colombia, France, Sweden, Norway, Denmark, and the Netherlands

Funding: see manuscript

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JOURNAL

PLoS Medicine

DOI

10.1371/journal.pmed.1004221 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

COI STATEMENT

Competing Interests: see manuscript

Socio-economic inequalities in access to joint replacement surgery in England

Peer-Reviewed Publication

PLOS

 

IMAGE: RESEARCHERS INVESTIGATED INEQUALITIES IN PROVISION OF JOINT REPLACEMENT FOR OSTEOARTHRITIS. view more 

CREDIT: TOWFIQU BARBHUIYA, PEXELS (CC0, HTTPS://CREATIVECOMMONS.ORG/PUBLICDOMAIN/ZERO/1.0/)

The provision of joint replacement surgery in England is subject to socio-economic inequalities, despite a years-long effort to reduce them. A study of hip and knee surgeries over a ten-year period, published April 27th in the open access journal PLOS Medicine, concludes that care providers must take further action to address variation in access to these frequently performed operations.

Joint replacements are cost-effective elective surgeries that are frequently performed in developed settings around the world. As populations age and obesity rises, the need for these surgeries is likely to increase, which will place an increasing public health burden on health systems. People living in the most deprived areas have the greatest need for surgery, and inequalities were reported in the UK over a decade ago. National Health Service (NHS) England has tried to address this, in part by delivering part of its publicly funded orthopedic activities within the private sector. With growing financial strain in the NHS, the current picture is unclear.

Erik Lenguerrand of the University of Bristol, UK, and colleagues merged data from the National Joint Registry and the Office for National Statistics official population statistics to investigate inequalities in provision of joint replacement for osteoarthritis. They identified all primary hip and knee replacements for osteoarthritis between 2007 and 2017 in England (675,342 hip and 834,146 knee replacements overall). Despite an overall improvement in the numbers of operations performed and less geographical variation in rates of surgery, inequalities between the most and least affluent areas remained large, and inequalities between most and least affluent areas have remained fairly constant.

For knee replacement, the social deprivation inequalities were only observed for the privately funded procedures, whereas for hip replacement, evidence of disparities was observed for both publicly and privately funded procedures. These findings could help healthcare commissioners to identify how joint replacement provision should be provided in the NHS to best address these disparities. One limitation was that this study was unable to investigate inequalities by certain important domains, such as ethnicity.

Lenguerrand adds, “Our study has shown that over the last decade socioeconomic inequalities in access to hip and knee replacement surgery remain wide, where those living in the most deprived areas have the least access to this surgery, even though they have the greatest clinical need.”

#####

In your coverage, please use this URL to provide access to the freely available paper in PLOS Medicine: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004210

Citation: Lenguerrand E, Ben-Shlomo Y, Rangan A, Beswick A, Whitehouse MR, Deere K, et al. (2023) Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007–2017: A population-based cohort study of the National Joint Registry. PLoS Med 20(4): e1004210. https://doi.org/10.1371/journal.pmed.1004210

Author Countries: United Kingdom

Funding: see manuscript

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JOURNAL

PLoS Medicine

DOI

10.1371/journal.pmed.1004210 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

COI STATEMENT

Competing Interests: see manuscript

Study suggests catalyst for human brain evolution

Large structural changes to the genomes of human ancestors could have spurred the smaller changes that set human brains apart from other primates

Peer-Reviewed Publication

GLADSTONE INSTITUTES

 

IMAGE: RESEARCHERS FROM GLADSTONE INSTITUTES KATIE POLLARD (RIGHT) AND KATHLEEN KEOUGH (LEFT) LED A STUDY THAT FOUND LARGE STRUCTURAL CHANGES TO THE GENOMES OF OUR ANCESTORS LIKELY SET OFF A CASCADE OF OTHER RAPID CHANGES IN HUMAN DNA THAT MAY UNDERLIE UNIQUELY HUMAN FEATURES, PARTICULARLY THE BRAIN. view more 

CREDIT: MICHAEL SHORT/GLADSTONE INSTITUTES

SAN FRANCISCO, CA—April 28, 2023—More than a million years ago, large chunks of the human genome were rearranged—a chance event during egg or sperm formation that led to the deletion, duplication, or reversal of sections of DNA. Those structural variants, researchers have now discovered, likely set off a cascade of other rapid changes in human DNA that may underlie uniquely human features, particularly the brain.

The new finding, published today in Science by researchers at Gladstone Institutes, came out of a study analyzing how stretches of DNA called human accelerated regions (HARs) differ between humans and chimpanzees. HARs are nearly identical among all humans, but differ between humans and all other mammals. Researchers have long wondered why these sequences—many of which control brain development—changed so rapidly in early human evolution.

“What we found is that many HARs are in regions of DNA where structural variants caused the genome to fold differently in humans compared to other primates,” says Katie Pollard, PhD, director of the Gladstone Institute of Data Science and Biotechnology and lead author of the new study. “This gave us an idea how HARs could have arisen in the first place.”

Folding like Origami

When comparing human and chimpanzee genomes nearly two decades ago, Pollard discovered regions of DNA—now called HARs—that were stable in mammals for millennia, but suddenly changed in early humans. Her lab has since shown that most HARs are enhancers, short stretches of DNA that regulate the activity of genes related to brain development. But researchers still have many questions about how HARs came about and the role they play in making humans distinct from other primates.

Pollard and her colleagues wondered whether other changes to the DNA surrounding HARs might help explain their origin. In collaboration with The Zoonomia Project, an international collaboration to study mammalian genomes, the researchers analyzed HARs and their surroundings in 241 mammalian genomes. They concluded that HARs tend to be located in areas of the human genome that have large structural differences when compared to other mammals.

So, the scientists next probed whether the structural variations around HARs might have changed the way the DNA folded.

“The way the genome folds up in three-dimensional space like origami is particularly important for enhancers,” explains Pollard, who is also a professor at UC San Francisco and a Chan Zuckerberg Biohub investigator. “That’s because enhancers can impact the activity of any gene that ends up close by, which can vary depending on how DNA is folded.”

To study the relationship between HARs and DNA folding, Pollard’s team used a machine learning model they previously developed to predict DNA folding patterns, and applied it to human and chimpanzee DNA sequences. Then, they identified the regions of the genome that folded differently in humans. The computer predicted that nearly 30 percent of HARs were in areas of the genome that folded differently in humans compared to chimpanzees.

“We realized that these human-specific structural changes may have created the right environment for HARs to evolve fast in the human ancestor, after remaining almost the same over millions of years of mammal evolution,” said Kathleen Keough, PhD, first author of the study and former postdoctoral scholar in the Pollard lab at Gladstone.

Piecing Together the Past

If DNA near HARs folded differently in humans and brought different genes in proximity to HARs, this could have had drastic consequences for our ancestors.

“Imagine you’re an enhancer controlling blood hormone levels, and then the DNA folds in a new way and suddenly, you’re sitting next to a neurotransmitter gene and need to regulate chemical levels in the brain instead of in the blood,” says Pollard. “Your instructions are now out-of-date and need to be changed.”

The predictions from the machine learning model suggested that large structural changes had occurred near HARs, but did not demonstrate which genes had fallen under their control. To address that question, Pollard and her colleagues carried out lab experiments that let them determine, in human and chimpanzee brain cells they derived from stem cells, what stretches of DNA were closest to hundreds of different HARs.

In many cases, they found, the human HARs were close to genes known to play a role in brain development; in some instances, the nearby genes were also associated with neurodevelopmental or psychiatric diseases.

Pollard’s team recently reported that the variations that rapidly appeared in HARs during early human evolution often opposed each other, first turning up the activity of an enhancer and then turning it down, or vice versa. The new results, she says, fit in well with the model proposed in that study.

“Something big happens like this massive change in genome folding, and our cells have to quickly fix it to avoid an evolutionary disadvantage,” said Pollard. “But the fix might kind of overdo it and need to be refined over time.”

While the new paper helps answer how HARs may have emerged in the beginning, Pollard’s team still has questions they plan to follow up on about why the massive structural changes survived the test of time and how HARs impact human brain development.

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About the Study

The paper “Three-dimensional genome re-wiring in loci with Human Accelerated Regions” was published in the journal Science on April 28, 2023.

Other authors are Sean Whalen and Pawel Przytycki of Gladstone; Fumitaka Inoue, Tyler Fair, Chengyu Deng, Marilyn Steyert, Hane Ryu, Tomasz Nowakowski, Nadav Ahituv, and Alex Pollen of UCSF; and Kerstin Lindblad-Toh and Elinor Karlsson of Broad Institute of Harvard and MIT.

The work was supported by a Discovery Fellowship, the National Institutes of Health (GR-01125,  DP2MH122400-01, NHGRI R01HG008742), the National Institute of Mental Health (R01MH109907, U01MH116438), the Schmidt Futures Foundation, the Shurl and Kay Curci Foundation, and a Swedish Research Council Distinguished Professor Award.

About Gladstone Institutes

Gladstone Institutes is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. Established in 1979, it is located in the epicenter of biomedical and technological innovation, in the Mission Bay neighborhood of San Francisco. Gladstone has created a research model that disrupts how science is done, funds big ideas, and attracts the brightest minds.

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JOURNAL

Science

DOI

10.1126/science.abm1696 

ARTICLE TITLE

Three-dimensional genome re-wiring in loci with human accelerated regions

ARTICLE PUBLICATION DATE

28-Apr-2023