Brain connectivity is disrupted in schizophrenia

Disruptions develop with diagnosed disease according to a new study published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Peer-Reviewed Publication

ELSEVIER

 

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BRAIN AREAS WITH THE GREATEST DIFFERENCE BETWEEN INDIVIDUALS WITH AND WITHOUT SCHIZOPHRENIA, WITH A PRONOUNCED NEGATIVE EFFECT IN VISUAL AREAS OF THE BRAIN.

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CREDIT: BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING

Philadelphia, October 17, 2023 – Schizophrenia, a neurodevelopmental disorder that features psychosis among its symptoms, is thought to arise from disorganization in brain connectivity and functional integration. Now, a new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, finds differences in functional brain connectivity in people with and without psychosis and schizophrenia that could help researchers understand the neural underpinnings of this disease.

The brain’s cortex is organized in a hierarchical fashion, anchored by the sensorimotor cortex at one end and by multimodal association areas at the other, with the task of integrating incoming sensory information with internal and external sensory signals. The loss of executive control in schizophrenia may stem from disruption of this hierarchical signaling.

Alexander Holmes, a PhD candidate at Monash University who led the study, said, “We used brain imaging and novel mathematical techniques to investigate the hierarchical organization of the brains of individuals with early psychosis and established schizophrenia. This organization is important for brain health, as it regulates how we can effectively respond to and process stimuli from the external world.”

The researchers used resting-state functional magnetic resonance imaging (fMRI) to measure gradients, an estimate of inter-regional functional coupling. Previous work had suggested that the primary sensory-fugal gradient was disrupted with schizophrenia, but the current study showed instead that secondary processing of the sensorimotor-visual gradient was affected in people with the disease.

Holmes added, “We found that the organizational pattern that differentiates visual and sensorimotor pathways is significantly impaired in individuals with schizophrenia but not in individuals with early psychosis. We then found that this impairment explains behavioral and clinical symptoms of schizophrenia. Our results highlight that changes in brain organization provide valuable insights into the mechanisms of schizophrenia, helping us better understand the disease and how it progresses.”

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the work, “These new approaches to test mathematical models of the organization of circuits in the human brain are beginning to reveal the nature of the disruption of neural integration that underlies psychotic symptoms in people with schizophrenia. Targeting these changes offers a new approach to how we think about developing treatments for this often difficult to treat illness.”

 

 

 

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JOURNAL

Biological Psychiatry Cognitive Neuroscience and Neuroimaging

DOI

10.1016/j.bpsc.2023.08.008 

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Disruptions of Hierarchical Cortical Organization in Early Psychosis and Schizophrenia

ARTICLE PUBLICATION DATE

6-Sep-2023

COI STATEMENT

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article. Cameron S. Carter, MD, is Professor of Psychiatry and Psychology and Director of the Center for Neuroscience at the University of California, Davis. His disclosures of financial and conflicts of interests are available at http://www.biologicalpsychiatrycnni.org/bpsc-editorial-disclosures.

 

AIP recognizes 2023 Andrew Gemant Award winner Sidney Perkowitz for contributions to physics and culture

Prize awarded to physicist and author for his work connecting art, the media, and literature to science

Grant and Award Announcement

AMERICAN INSTITUTE OF PHYSICS

 

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SIDNEY PERKOWITZ, WINNER OF THE 2023 ANDREW GEMANT AWARD

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CREDIT: PERKOWITZ

WASHINGTON, Oct. 17, 2023 – AIP is pleased to announce Sidney Perkowitz as the winner of the 2023 Andrew Gemant Award, presented to those who have made significant contributions to the cultural, artistic, or humanistic dimension of physics.  

Perkowitz was chosen by the award selection committee for his enduring commitment to bridge the physics community with the arts and humanities by using a variety of media—including books, essays, public lectures, and theatrical productions. 

“Dr. Perkowitz exemplifies the values of this award through this impressive and diverse body of work,” said AIP CEO Michael Moloney. “Using art and literature to communicate science, he finds a common ground by which we can all better access and ponder the wonders of our world that physics reveals.” 

Growing up in Brooklyn, New York, Perkowitz always knew he would be a scientist, but that did not stop him from also dreaming about being a writer. Now, he has authored or edited 11 books, written more than 200 articles and essays, and created four screenplays and scripts, as well as the text for four museum exhibits. He also engages with audiences directly through public lectures.  

“I always wanted to be a scientist,” Perkowitz said. “I can’t give any origins for it — I’m not only the first scientist in my family, I’m among the first college graduates. But at the same time, my other choice was always to be a writer. Somehow, the two interests merged.” 

Perkowitz started his prolific career as a physicist. He attended the Polytechnic Institute University of Brooklyn, now New York University Tandon School of Engineering, where he received a bachelor’s degree in physics, and earned his doctorate in solid state physics from the University of Pennsylvania.  

While at Emory University, where he had become the Charles Howard Candler Professor of Physics, he achieved two major milestones in one year, publishing his 100th research paper and reaching his 50th birthday.  

It was at this moment he realized he could do more to advocate for physics. Generous colleagues at Emory supported his efforts as he started writing books, lectures, essays, and exhibit texts that combine physics with art, literature, and history.  

“One great advantage that comes from being raised in New York is that you’re in one of the art capitals of the world. As a high school and college student, just because of personal interest, I was exposed to a lot of art,” Perkowitz said. “My first book, ‘Empire of Light,’ was about the connection between science and art. It became apparent that once you think about science this way, it should be considered part of everything we count as culture: science, art, music, reading, and writing. These are human activities, and science is one of them.” 

For many years, Perkowitz pursued science communication while still completing his duties as a physics professor and researcher. He believes that scientific outreach is crucial for maintaining a healthy society and a rich culture. 

“Winning this award means a lot to me personally,” said Perkowitz. “If you look at the list of people also awarded this, I’m in admirable company. I’m really honored to be included in this group. 

“On a higher level, I think about what this award means for physics. I think it is wonderful that AIP administers an award that is all about making physics and science more open and more popular to the whole world. If scientists don’t talk to society, society is not going to trust us or support us.” 

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About the Award 

The Andrew Gemant Award recognizes the accomplishments of a person who has made significant contributions to the cultural, artistic, or humanistic dimension of physics and is given annually. The award is made possible by a bequest of Andrew Gemant to the American Institute of Physics. 

The awardee receives a $5,000 cash award, designates an academic institution to receive a grant of $3,000 to further the public communication of physics, and is invited to deliver a public lecture in a suitable forum. 

ABOUT AIP 

The mission of AIP (American Institute of Physics) is to advance, promote, and serve the physical sciences for the benefit of humanity. AIP is a federation that advances the success of our 10 Member Societies and an institute that operates as a center of excellence supporting the physical sciences enterprise. In its role as an institute, AIP uses policy analysis, social science, and historical research to promote future progress in the physical sciences. AIP is a 501(c)(3) membership corporation of scientific societies.  

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Study examines role of working memory, cognitive functions in English learners learning to write

Research among first to gauge how students learn to write in second language, can help design interventions

Peer-Reviewed Publication

UNIVERSITY OF KANSAS

LAWRENCE — When a person attempts to express their thoughts in writing, they use a series of cognitive functions like working memory to access words and ideas they want to convey, phonological awareness of concepts such as syntax and more. And that is in their native language. A new study from the University of Kansas is among the first of its kind to examine cognitive functions and their role in teaching English learners to write in their second language, which can help shed light on how students learn to write and how to help close the achievement gap in the growing Hispanic English learning population’s writing abilities.

The study performed a battery of bilingual cognitive tests with nearly 500 elementary-age English learners and found the relationships between English writing performance and cognitive skills became stronger as grades increased. However, the relationships between English writing and Spanish cognitive and reading determinants were mixed, indicating working memory capacity was especially important in the population’s performance in learning to write in their second language. The findings not only shed light on how students learn to write, they could help lead to development of interventions to help English learners improve their writing abilities.

Researchers performed tests to determine a group of English learner students’ aptitude in three cognitive and reading areas related to their native Spanish and English: phonological awareness, oral language development and working memory. They also tested their writing abilities in English as they progressed through first through third grades.

“We found working memory was the most significant predictor of writing ability. Within each test, there were multiple items that assessed the students’ performance in the cognitive functions we were studying and their English writing,” said Hui Wang of McKendree University, a recent KU doctoral graduate from the Department of Educational Psychology and lead author of the study. “There are about 5 million English learners in the United States, and 3.8 million of them are Hispanic, but very little research has been done on how this population learns to write.”

American education has focused largely on reading and math, both for English learners and as a whole in recent decades. Yet writing is frequently used to determine how well students understand a topic.

Michael Orosco, professor of educational psychology and one of the study authors, has long researched how English learners perform in schools and the cognitive functions that take part in learning reading, math and other subjects. He and colleagues have recently studied the populations’ reading writing and cognitive performance and how a lack of instruction in their native language hinders their learning to read in English.

“I told an assistant school superintendent of learning, ‘We should pull out these kids and assess their writing abilities.’ If we can’t look at how they’re developing, we’re not going to be able to design interventions and practices to help them improve,” Orosco said. “Children who are bilingual appear to have an enhanced working memory due to their bilingualism. While it's an underlying trait that isn't directly visible, it's crucial for retaining and retrieving information, especially during writing.”

Working memory, phonological awareness and oral language development were measured in all students in both Spanish and English as they progressed through grades using a battery of bilingual assessments. Students’ writing abilities were also regularly assessed. Students’ performance in all of the cognitive skills, as well as writing performance, increased as they progressed among the grades. However, only working memory consistently predicted higher scores in writing. Orosco said that this underscores the significance of working memory, particularly the ability to quickly recall vocabulary and concepts while writing. It also implies that without native language instruction in schools, students may not be enhancing their oral language development and phonological awareness skills, despite having innate strengths in their native language, he said.

The study, written with co-authors Anqi Peng, educational psychology doctoral candidate at KU; Haiying Long, professor of educational psychology at KU; Deborah Reed of the University of Tennessee; and H. Lee Swanson of the University of New Mexico, was published in the Journal of Experimental Child Psychology.

Orosco, who is also director of the Center for Culturally Responsive Educational Neuroscience in KU’s Achievement & Assessment Institute, said the findings emphasize the importance of understanding how students learn to write and also shed light on how the brain processes information, especially for bilingual learners.

"Neuroscience reveals that working memory is a complex cognitive function involving multiple regions. The prefrontal cortex is central to working memory, handling the retention and manipulation of short-term information. For bilingual individuals, this executive functioning region aids in merging linguistic structures and vocabulary from different languages, thereby boosting their bilingual working memory, which is vital for writing effectively," Orosco said. "Our understanding of enhancing students' writing skills has deepened. By bolstering their oral language and phonological awareness, we also appear to boost their working memory capacity. This increased capacity to retain and manage information is invaluable in guiding students in writing."

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JOURNAL

Journal of Experimental Child Psychology

DOI

10.1016/j.jecp.2023.105776 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The relation of bilingual cognitive skills to the second language writing performance of primary grade students

ARTICLE PUBLICATION DATE

16-Oct-2023

 

Race and ethnicity and prehospital use of opioid or ketamine analgesia in acute traumatic injury

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK

About The Study: The results of this study of over 4.7 million patient encounters across the U.S. during a 3-year period suggest that patients from racial and ethnic minority groups with acute traumatic injuries do not have their pain treated equitably in the prehospital setting.

Authors: Eli Carrillo, M.D., of the Stanford University School of Medicine in Stanford, California, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi: 10.1001/jamanetworkopen.2023.38070)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Embed this link to provide your readers free access to the full-text article

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About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

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Effects of the million hearts model on heart attacks, strokes, and Medicare spending

JAMA

Peer-Reviewed Publication

JAMA NETWORK

About The Study: The Million Hearts Model, which encouraged and paid health care organizations to assess and reduce cardiovascular disease (CVD) risk, reduced first-time heart attacks and strokes. The results support guidelines to use risk scores for CVD primary prevention. 

Authors: Laura Blue, Ph.D., of Mathematica in Washington, D.C., is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2023.19597)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article

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JOURNAL

JAMA

 

Researchers receive NIH grant to improve quality of life for people with Down syndrome

Grant and Award Announcement

TEXAS A&M UNIVERSITY

 

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GARHETT WYATT, POSTDOCTORAL RESEARCHER, AND WESTON PORTER

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CREDIT: JASON NITSCH/TEXAS A&M UNIVERSITY DIVISION OF MARKETING AND COMMUNICATIONS

A team of researchers at the Texas A&M University School of Veterinary Medicine & Biomedical Sciences (VMBS) has received a grant from the National Institutes of Health (NIH) to research metabolism in people with Down syndrome.

By targeting genes that affect metabolism, the team may be able to develop drug therapies for physical and mental symptoms of the condition, like muscle loss, accelerated aging, and lower cognitive function, thereby improving the quality of life for people with Down syndrome.

The new grant will also make Dr. Weston Porter, a professor in the VMBS Department of Veterinary Physiology & Pharmacology and lead researcher on the project, one of the highest NIH-funded researchers at Texas A&M.

Making Connections

Down syndrome is a genetic condition that affects approximately 1 in every 700 fetuses and can cause varying degrees of physical, mental, and developmental disability. There are currently about 400,000 people with Down syndrome living in the United States.

Porter’s interest in studying Down syndrome came by way of breast cancer research, which he’s been conducting for over 20 years.

“Part of our lab team works on a protein called SIM2 and its relationship to breast cancer,” Porter said. “SIM2 happens to be in the middle of a section of chromosome 21 that we call the ‘Down syndrome-critical region.’ Almost every individual with Down syndrome has an extra copy of this gene.”

Genetic conditions like Down syndrome are closely linked with changes in tumor and cancer profiles, like breast cancer, according to Porter.

“Primarily, we see an increase in tumor incidents in individuals with genetic diseases. For example, people with Down syndrome are more likely to develop leukemias and lymphomas. However, breast cancer is extremely rare for these individuals,” he said.

Porter and his team of researchers have previously been awarded grants to study the intersection of breast cancer and Down syndrome. The team studied the role of SIM2 in providing people with Down syndrome increased resistance to breast cancer because of Down syndrome’s triplication of certain genes.

“Having SIM2 offers a sort of protective mechanism against breast cancer, but the over-expression of SIM2 leads to the development of other health concerns,” said Lilia Sanchez, a graduate student in Porter’s lab. “Our goal is to better understand the role SIM2 plays and also how much is too much so that we can develop therapies that help combat diseases related to both the over- and under-expression of SIM2.”

The lab’s research into the connection between breast cancer and SIM2 led them to believe that the protein might also be involved in regulating crucial metabolic factors in Down syndrome.

“Many of the phenotypic elements of Down syndrome — the physical and mental manifestations like muscle loss, increased chance of Alzheimer’s and Parkinson’s diseases, developmental disability — are linked to changes in metabolism,” Porter said. “The reason for this is that the cells’ mitochondria, which help regulate metabolism, are constantly running at full steam in Down syndrome. It’s like running the car engine all the time.”

Likewise, the changes in metabolism that people with Down syndrome experience come from having an overexpression of SIM2.

“When SIM2 is overexpressed, we see that it ramps up the mitochondria — you’re turning it on, but you cannot turn it back off,” he said. “That results in mitochondrial dysfunction.”

Multi-faceted Mitochondria

Contrary to what most people remember from high school, mitochondria aren’t just powerhouses for cells. They play a role in a number of cellular processes, which is one reason that metabolism is so interconnected with Down syndrome.

Sanchez has published researched describing how SIM2 regulates mitochondria during periods of stress. Her research examined SIM2’s role in regulating mitochondrial health in breast tissues during lactation, which is a stressful time for mammary cells.

“The main takeaway from this paper is that mitophagy, which is the recycling of mitochondria, is a normal process that naturally happens in tissues that are highly active,” Sanchez said. “Mitophagy is also involved in the stress response of the cell, and our data suggest that SIM2 regulates the rapid recycling of mitochondria, thus enhancing functions accompanied by higher stress, such as lactation.”

SIM2 also impacts mitochondria in other ways, according to Dr. Steven Wall, a former graduate student in Porter’s lab.

“SIM2’s role in electron transport is the most novel thing we found,” said Wall, who served as the lead author for another publication produced by the lab. “Previously, it was not known to be involved in the electron transport chain, yet we found it consistently in the mitochondria and in the electron transport chain.”

Since the electron transport chain is a fundamental part of how the mitochondria regulates energy, it’s clear that SIM2 has the ability to regulate some of the most important functions within our cells.

Combined with SIM2’s rapid recycling effect on mitochondria, it also appears to be crucial for understanding Down syndrome.

Transforming Life With Down Syndrome

While the new grant will specifically look at SIM2’s role in regulating skeletal muscle metabolism, Porter also hopes that the project will lead to studies of other parts of the body and will eventually make new therapies available to people with Down syndrome.

“Given the amount of research happening on genetic diseases right now, it’s becoming much more possible to develop drugs for those diseases,” he said. “Working with Down syndrome is tricky because there are 20 to 30 genes changing, but, incrementally, we hope to improve people’s quality of life.”

Porter and his team are also developing ways to involve the Down syndrome community in offering feedback and ideas for future research directions.

“We want to know their concerns so that we can prioritize research that addresses them,” he said. “They can help us decide which aspects of life with Down syndrome to focus on next in our research — things like improved mobility, cognitive function, or life expectancy.”

Ultimately, Porter believes the new study will have a big impact for people with Down syndrome.

“It’s going to be transformative,” Porter said.

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By Courtney Price, Texas A&M University School of Veterinary Medicine and Biomedical Sciences

 

Researchers receive $423,500 for study to improve outcomes from fungal infections

Grant and Award Announcement

UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER

 

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BRIAN PETERS, PHD, AND JARROD FORTWENDEL, PHD

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CREDIT: UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER

Aspergillus fumigatus is the major airborne fungus present indoors and outdoors that causes various diseases, the severity of which are dependent on an individual’s immune status. 

Researchers in the College of Pharmacy at the University of Tennessee Health Science Center have received a $423,500 grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health for research aimed at reducing disease and mortality rates associated with Aspergillus infections by focusing on the molecular pathways in the fungus that mediate inflammatory host responses.

Jarrod Fortwendel, PhD, professor and director of the Center for Pediatric Experimental Therapeutics in the Department of Clinical Pharmacy and Translational Science, and Brian Peters, PhD, associate professor and First Tennessee Endowed Chair of Excellence in Clinical Pharmacy in the Department of Clinical Pharmacy and Translational Science, are the principal investigators of this study.

“Aspergillus fumigatus is a filamentous fungal pathogen that causes disease in a wide range of individuals. Most of the at-risk population have a dysfunctional immune system. In the severely immune suppressed, Aspergillus causes invasive disease that’s considered highly deadly,” Dr. Fortwendel said. “It also causes chronic diseases in individuals who may have a hyperactive immune system. In many of these cases, disease symptomology is driven by an overactive immune system that isn’t effective at clearing the fungus.”

In this collaboration between the labs of Dr. Fortwendel and Dr. Peters, the team will use a new genetic tool to identify molecular targets, or kinases, in the fungus that modify host-pathogen interactions to discover a method to assist the immune system to recognize and clear the fungus.

“It’s an airborne fungus that we inhale and, in at-risk individuals, invades the lung tissue and then disseminates throughout the body. Part of that process happens because the immune system is not functional enough to detect the pathogen,” Dr. Fortwendel said. “The study is designed to identify pathways that may be important for both immune-suppressed individuals and for those who are in hyper-inflammatory states when they encounter this organism.”

Although the current award is focused on helping to improve outcomes for patients suffering from Aspergillus infections, the team aims to apply their studies to other fungal infections as well. With their findings, they hope to contribute to future development of novel therapeutic approaches for initiating protection from invasive fungal infections and decrease the severity of harmful host-response during chronic infections.

“It is exciting to share the grant with a close colleague and collaborator. Our work will help delineate mechanisms, both on the host and the fungal side, that really contribute to immune system function and detection of Aspergillus,” Dr. Peters said.

“Sometimes too little inflammation is bad, and sometimes too much is bad, so the work will begin to define fungal kinases that are important for controlling both of those processes and give us an opportunity to target both sides,” Dr. Peters said. “And these immunomodulatory therapies are something that’s currently being talked about in the field as the next generation of therapeutic approaches to better manage fungal disease.”

 

What drives obesity - diets high in fat? Carbohydrates? Actually, it’s everything – and fructose is at the center

A new study led by CU Anschutz researcher Richard Johnson, MD, unifies a number of hypotheses behind the dietary cause of obesity that once seemed incompatible

Peer-Reviewed Publication

UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

AURORA, Colo. (October 17, 2023) – Nutrition experts have recognized for many years that western diets rich in fats and sugar may be behind the cause of obesity, but debate has reigned over the primary culprit - intake of too many calories? Specific foods such as carbohydrates or fat? This has led to some groups recommending reducing sugar, some reducing carb intake, while others believe the key is reducing high fat-foods. 

A paper published today in the research journal Obesity suggests these theories are not incompatible with each other, and that they can all be brought together in one unified pathway that centers around one true driver: fructose.

According to Richard Johnson, MD, University of Colorado Anschutz Medical Campus researcher, and his colleagues, the primary problem in obesity is fructose, which is present in table sugar and high fructose corn syrup. Fructose can also be made in the body from carbohydrates (particularly glucose). When fructose is metabolized, it lowers the active energy in the body (known as ATP, or adenosine triphosphate) which causes hunger and food intake.

What Johnson calls the “fructose survival hypothesis” brings together most of the dietary hypotheses of obesity, including the two that have been most incompatible with each other– the energy balance theory, which proposes too much food (and primarily fat) drives obesity, and the carbohydrate-insulin model, which puts carbohydrates at the center of weight gain.

“Essentially, these theories, which put a litany of metabolic and dietary drivers at the center of the obesity epidemic, are all pieces of a puzzle unified by one last piece: fructose,” says Johnson. “Fructose is what triggers our metabolism to go into low power mode and lose our control of appetite, but fatty foods become the major source of calories that drive weight gain.”

To unify these theories in particular, Johnson says we can look to hibernating animals as an example. When we’re hungry and low on active energy, we go into survival mode. Animals know to forage for food when energy levels begin to fall; why bears eat fruit to prepare for winter. Fruits are high-fructose foods, and fructose significantly stifles active energy. Fat acts as stored energy, but eating high-fructose foods blocks the replacement of active energy from fat storage, keeping active energy low like a bear preparing for a long winter’s nap.

“This theory views obesity as a low-energy state,” says Johnson. “Identifying fructose as the conduit that redirects active energy replacement to fat storage shows that fructose is what drives energy imbalance, which unites theories.”

While more work is needed to fully validate this unifying hypothesis, this is a hopeful first step in potentially identifying more targeted preventions for obesity and related metabolic imbalance management.

About the University of Colorado Anschutz Medical Campus

The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - that treat more than two million adult and pediatric patients each year. Innovative, interconnected and highly collaborative, the University of Colorado Anschutz Medical Campus delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by over $690 million in research grants. For more information, visit www.cuanschutz.edu.

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JOURNAL

Obesity

DOI

10.1002/oby.23920 

ARTICLE TITLE

The fructose survival hypothesis as a mechanism for unifying the various obesity hypotheses

 

Multi-drug resistant strain of E.coli battles bacteria in healthy gut

Peer-Reviewed Publication

UNIVERSITY OF BIRMINGHAM

Different strains of E.coli can outcompete one another to take over the gut, a new study reveals.

Publishing their findings today in PLOS Biology, scientists reveal that a particular strain, known as MDR ST131, can readily colonise new hosts, even if those hosts are already have E.coli in their healthy gut.

The international team, led by experts at the University of Birmingham, used a mouse model to help understand why strains of E.coli that live in a healthy gut are rapidly overtaken of when challenged with a multi-drug resistant strain.

Lead author Professor Alan McNally, from the Institute of Microbiology and Infection at the University of Birmingham, commented: “Antibiotic resistance has been hailed as one of the biggest health problems of our time by the World Health Organisation. There are further problems looming unless we get a better understanding of what is happening so that further drug resistance can be halted in its tracks.

“Scientists have long questioned what makes certain types of E. coli successful multi-drug resistant pathogens. It seems that extra-intestinal pathogenic E.coli, which cause urinary tract and bloodstream infections, are particularly successful when it comes to developing resistance and are therefore especially tricky to treat. Our study provides evidence that certain types of E.coli are more prone to develop antibiotic resistance than others.”

Most cases of E. coli infections are mild, but some strains can cause severe symptoms and even life-threatening complications. More severe infections are usually treated with antibiotics but the rise in multidrug resistance strains of E.coli is concerning. Multidrug-resistant strains are resistant to many different types of antibiotics, making them very difficult to treat.

Previous work shows that multi-drug resistance alone is not sufficient to drive strains to complete dominance. This most recent study demonstrates that regardless of multi-drug resistant status, certain types of E.coli will outcompete others to live in the human gut.

The work was completed in parts. First, both multi-drug resistant and non-resistant gut-dwelling E.coli were found to easily colonise a mammalian gut. In a second part of the study, the multi-drug resistant strain was found to efficiently displace an already established gut-dwelling E.coli from the mouse intestinal tract. The study provided further details to demonstrate that multidrug resistant lineages of extraintestinal E.coli have particular genetic differences that appear to give them a competitive advantage.

Successful strains of E.coli need to be able to spread between individuals or from the environment into individual hosts. The new study demonstrates that a particular strain, known as MDR ST131, can readily colonise new hosts, even if those hosts are already have E.coli in their healthy gut.

E.coli are bacteria commonly found in the environment, foods and intestines of people and animals. There are many different types of E. coli. Although most strains of E. coli are harmless, others can cause illness, including diarrhoea, urinary tract infections, and often-fatal blood stream infections.

ENDS

For more information or interviews, please contact Tony Moran, International Communications Manager, University of Birmingham on +44 (0)782 783 2312 or t.moran@bham.ac.uk. Out-of-hours please call +44 (0)121 414 2772.

Notes to Editors

• The University of Birmingham is ranked amongst the world’s top 100 institutions, its work brings people from across the world to Birmingham, including researchers and teachers and more than 8,000 international students from over 150 countries.
• ‘Multi-drug resistant E. coli encoding high genetic diversity in carbohydrate metabolism genes displace commensal E. coli from the intestinal tract’ - Christopher H. Connor, Amanda Z. Zucoloto, John Munnoch, Ian-Ling Yu, Jukka Corander, Paul Hoskisson, Braedon McDonald, and Alan McNally is published by PLOS Bio.
• Participating institutions include: The University of Birmingham, UK; University of Calgary, Canada; University of Strathclyde, Glasgow, UK; University of Oslo, Norway; Wellcome Sanger Institute, Cambridge, UK; and University of Helsinki, Finland.

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JOURNAL

PLoS Biology

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Multi-drug resistant E. coli encoding high genetic diversity in carbohydrate metabolism genes displace commensal E. coli from the intestinal tract

ARTICLE PUBLICATION DATE

17-Oct-2023

Disclaimer: AAAS a

 

Sleep and stress give clues to understanding epileptic seizures - study

Peer-Reviewed Publication

UNIVERSITY OF BIRMINGHAM

Sleeping patterns and stress hormones could be the key to understanding how and when people with epilepsy are likely to experience seizures, a new study reveals. 

Researchers used mathematical modelling to understand the impact of different physiological processes, such as sleep and changes in concentration of the stress-hormone cortisol, on key signatures of epilepsy – known as epileptiform discharges (ED).

Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous seizures. Classically, seizures were assumed to occur at random, until the discovery of ED activity with timescales that vary from hours and days through to months.

The scientists analysed 24-hour EEG recordings from 107 people with idiopathic generalized epilepsy and discovered two subgroups with distinct distributions of epileptiform discharges: one with highest incidence during sleep and the other during daytime.

Publishing their findings in PLOS Computational Biology, the international research team led by the University of Birmingham, reveal that either the dynamics of cortisol or sleep stage transition, or a combination of both, explained most of the observed distributions of ED.

Lead author Isabella Marinelli, from the University of Birmingham’s Centre for Systems Modelling & Quantitative Biomedicine (SMQB), commented: “Some 65 million people have epilepsy worldwide, many of whom report specific triggers that make their seizures more likely - the most common of which include stress, sleep deprivation and fatigue.

“Our findings provide conceptual evidence that sleep patterns and changes in concentration of cortisol are underlying physiological drivers of rhythms of epileptiform discharges. Our mathematical approach provides a framework for better understanding what factors facilitate the occurrence of ED activity and potentially trigger the seizures which can be so debilitating for epilepsy sufferers.”

The researchers’ mathematical model describes the activity of connected brain regions, and how the excitability of these regions can change in response to different stimuli - either transitions between sleep stages or variation in concentration of cortisol.

ED frequency increases during the night, early in the morning, and in stressful situations in many people with epilepsy. The team discovered that sleep accounted for 90% of variation in one subgroup and cortisol around 60% in the other subgroup.

Cortisol is one of the primary stress hormones in humans, with production and secretion controlled by the hypothalamic-pituitary-adrenal (HPA)-axis. In stressful situations, HPA-axis activity increases, resulting in a higher secretion of cortisol.

“Sleep alone cannot account for the changes in ED likelihood during wakefulness observed in our first subgroup,” explained Dr Marinelli. “There is a reduction in ED likelihood during the sleep time after an initial sharp increase during the first hours.

“This can be explained by the fact that deep sleep, which is linked to an increase of EDs, is predominant during the first third of the sleep period. We found an increase in ED occurrence before waking, which - given that the level of cortisol is known to increase around waking - suggests a combined effect of sleep and cortisol.”

ENDS

For more information, interviews or an embargoed copy of the research paper, contact Tony Moran, International Communications Manager or call +44 (0)7827 832312 email t.moran@bham.ac.uk or pressoffice@contacts.bham.ac.uk

Notes for editors

• The University of Birmingham is ranked amongst the world’s top institutions, its work brings people from across the world to Birmingham, including researchers and teachers and more than 8,000 international students from over 150 countries.
• ‘Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability’ - Isabella Marinelli, Jamie J. Walker, Udaya Seneviratne, Wendyl D’Souza, Mark J. Cook, Clare Anderson’, Andrew P. Bagshaw, Stafford L. Lightman, Wessel Woldman, and John R. Terry is published in PLOS Computational Biology.
• Participating institutions include: University of Birmingham, UK; University of Exeter, UK; University of Melbourne, Australia; Monash University, Australia; and University of Bristol, UK.
• The Centre for Systems Modelling and Quantitative Biomedicine (SMQB) is a unique interdisciplinary collaborative spanning mathematics, computer science and medicine. It was established in 2019 through a strategic investment of £7 million by the University of Birmingham (www.birmingham.ac.uk/smqb).

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JOURNAL

PLoS Computational Biology

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability

ARTICLE PUBLICATION DATE

17-Oct-2023