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Biochemistry

“Unlocking Hidden Risks: How MRI Scans Can Revolutionize the Detection of Life-Threatening Heart Disease”

Magnetic resonance imaging (MRI) scans of the heart could help to detect a life-threatening heart disease and enable clinicians to better predict which patients are most at risk, according to a new study.

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Lamin Heart Disease: A Hidden Killer

Lamin heart disease is a rare but potentially life-threatening condition that affects the heart’s ability to pump blood. It’s caused by a genetic mutation in the LMNA gene, which produces proteins essential for heart cell function. This condition often goes undiagnosed, affecting people in their 30s and 40s.

A new study led by researchers at University College London (UCL) has found that MRI scans can detect hidden signs of lamin heart disease, even when other tests show a healthy heart. The findings suggest that MRI could revolutionize the way we predict which patients are most at risk and inform decisions about life-changing treatments like heart transplants or implantable defibrillators.

Currently, risk estimates are based on electrocardiograms (ECGs), patient sex, genetics, symptoms, and basic heart function measurements by ultrasound. However, this tool underperforms for women and often recommends unnecessary devices that can be life-changing but not beneficial. The new study reveals the potential of cardiac MRI to improve disease risk predictions and become a standard part of managing lamin heart disease.

“Genetics alone cannot predict how this disease will progress,” said Dr. Gaby Captur, senior author of the study. “Two people with the same variant can have completely different outcomes.”

Lead author Dr. Cristian Topriceanu added, “Cardiac MRI picks up scarring of the heart tissue, inflammation, and signs the heart muscle is not working as well as it should among carriers of an LMNA mutation who do not have more overt signs of disease.”

These findings suggest a potential role for MRI in tracking disease progression and response to treatment. Gene therapies currently being trialled could tackle the cause of lamin heart disease, and MRI can identify people with early-stage disease displaying subtle abnormalities suggesting their disease is progressing.

The LMNA gene instructs the body to make proteins lamin A and C, critical to the structure and stability of heart cell nuclei. Mutations can lead to problems like dilated cardiomyopathy, life-threatening heart rhythms, and disrupted electrical signals regulating the heartbeat.

Close family members of individuals with lamin disease are screened for an LMNA mutation, but carriers usually only receive follow-up ECGs and echocardiograms. The new study suggests that cardiac MRI could become a standard tool in this process, providing earlier detection and more accurate risk assessments.

The research team analyzed MRI data from 187 people, finding heart damage, inflammation, and scarring central to lamin heart disease but not present in non-genetic dilated cardiomyopathy. Participants with a specific LMNA mutation showed worse heart functioning, highlighting the importance of cardiac MRI in understanding the mechanics of the heart.

This study has significant implications for the management of lamin heart disease, potentially revolutionizing the way we detect and treat this condition. As Dr. Captur noted, “Our findings show the potential of cardiac MRI to improve disease risk predictions and become a standard part of how we manage lamin heart disease.”

The study received funding from various organizations, including the British Heart Foundation, the National Institute of Health and Care Research (NIHR), Barts Charity, the Society for Cardiovascular Magnetic Resonance, and the NIHR UCLH Biomedical Research Centre.

In conclusion, the findings of this study highlight the importance of cardiac MRI in detecting hidden risks associated with lamin heart disease. This technology has the potential to revolutionize the way we predict which patients are most at risk and inform decisions about life-changing treatments like heart transplants or implantable defibrillators. As research continues to uncover the secrets of lamin heart disease, it’s clear that cardiac MRI will play a vital role in this journey.

Biochemistry

A Game-Changing mRNA Vaccine that’s More Effective and Less Costly to Develop

A new type of mRNA vaccine is more scalable and adaptable to continuously evolving viruses such as SARS-CoV-2 and H5N1, according to a new study.

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A team of researchers from the University of Pittsburgh School of Public Health and Pennsylvania State University has made a groundbreaking discovery in the field of vaccine development. They have created a new type of mRNA vaccine that is not only more effective but also less costly to develop, making it a game-changer in the fight against infectious diseases.

The current mRNA vaccines, such as those used to prevent COVID-19, have two significant challenges: they require a high amount of mRNA to produce and are constantly evolving due to the changing nature of viruses like SARS-CoV-2 and H5N1. The researchers addressed these challenges by creating a proof-of-concept COVID-19 vaccine using what’s known as a “trans-amplifying” mRNA platform.

In this approach, the mRNA is separated into two fragments: the antigen sequence and the replicase sequence. The latter can be produced in advance, saving crucial time in the event of a new vaccine needing to be developed urgently and produced at scale. Additionally, the researchers analyzed the spike-protein sequences of all known variants of SARS-CoV-2 for commonalities, rendering what’s known as a “consensus spike protein” as the basis for the vaccine’s antigen.

The results are promising: in mice, the vaccine induced a robust immune response against many strains of SARS-CoV-2. This has the potential for more lasting immunity that would not require updating, because the vaccine has the potential to provide broad protection. Additionally, this format requires an mRNA dose 40 times less than conventional vaccines, so this new approach significantly reduces the overall cost of the vaccine.

The lessons learned from this study could inform more efficient vaccine development for other constantly evolving RNA viruses with pandemic potential, such as bird flu. The researchers hope to apply the principles of this lower-cost, broad-protection antigen design to pressing challenges like bird flu, making it a crucial step in preparing for future pandemics.

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Aerospace

Unveiling the Molecular Link Between Air Pollution and Pregnancy Risks: A Groundbreaking Study

A new study found exposure to specific tiny particles in air pollution during pregnancy are associated with increased risk of various negative birth outcomes.

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The air we breathe has long been a concern for public health, but a recent study by Emory University researchers sheds light on a specific and alarming link between air pollution and pregnancy risks. Published in Environmental Science & Technology, the research reveals that exposure to tiny particles in air pollution during pregnancy can disrupt maternal metabolism, leading to increased risk of various negative birth outcomes.

The study analyzed blood samples from 330 pregnant women in the Atlanta metropolitan area, providing a detailed insight into how ambient fine particulate matter (PM2.5) affects the metabolism of pregnant women and contributes to increased risks of preterm and early term births. This pioneering work marks the first time researchers have been able to investigate the specific fine particles responsible for these adverse outcomes.

“The link between air pollution and premature birth has been well established, but for the first time we were able to look at the detailed pathway and specific fine particles to identify how they are reflected in the increased risk of adverse birth outcomes,” says Donghai Liang, PhD, study lead author and associate professor of environmental health. “This is important because if we can figure out the ‘why’ and ‘how,’ then we can know better how to address it.”

Previous research has shown that pregnant women and fetuses are more vulnerable than other populations to exposure to PM2.5, which is emitted from combustion sources such as vehicle exhaust, industrial processes, and wildfires. This increased vulnerability is linked to a higher likelihood of preterm births, the leading cause of death globally among children under the age of five.

Preterm birth is associated with complications such as cerebral palsy, respiratory distress syndrome, and long-term noncommunicable disease risks. Early term births (37-39 weeks of gestation) are also linked to increased neonatal morbidity and developmental challenges. Approximately 10% of preterm births worldwide are attributable to PM2.5 exposure.

As an air pollution scientist, Liang emphasizes the importance of addressing this issue beyond simply asking people to move away from highly polluted areas. “From a clinical intervention standpoint, it’s critical to gain a better understanding on these pathways and molecules affected by pollution,” he says. “In the future, we may be able to target some of these molecules to develop effective strategies or clinical interventions that could help reduce these adverse health effects.”

This groundbreaking study highlights the urgent need for policymakers and healthcare providers to take action against air pollution, particularly in areas with high levels of PM2.5 exposure. By understanding the molecular link between air pollution and pregnancy risks, we can work towards developing targeted solutions to mitigate these negative outcomes and protect the health of future generations.

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Biochemistry

Bringing Clarity to Cancer Genomes with SAVANA: A Machine Learning Algorithm for Long-Read Sequencing

SAVANA uses a machine learning algorithm to identify cancer-specific structural variations and copy number aberrations in long-read DNA sequencing data. The complex structure of cancer genomes means that standard analysis tools give false-positive results, leading to erroneous clinical interpretations of tumour biology. SAVANA significantly reduces such errors. SAVANA offers rapid and reliable genomic analysis to better analyse clinical samples, thereby informing cancer diagnosis and therapeutic interventions.

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SAVANA is a groundbreaking algorithm that uses machine learning to accurately identify structural variants and copy number aberrations in cancer genomes. This innovative tool has been developed to overcome the limitations of existing analysis tools, which often fall short when analyzing long-read sequencing data. The complex structure of cancer genomes means that standard analysis tools can lead to false-positive results and unreliable interpretations of the data.

Researchers at EMBL’s European Bioinformatics Institute (EMBL-EBI) and the R&D laboratory of Genomics England have developed SAVANA in collaboration with clinical partners at University College London (UCL), the Royal National Orthopaedic Hospital (RNOH), Instituto de Medicina Molecular João Lobo Antunes, and Boston Children’s Hospital. The algorithm was tested across 99 human tumour samples and has shown remarkable accuracy in distinguishing between true cancer-related genomic alterations and sequencing artefacts.

“SAVANA changes the game,” said Isidro Cortes-Ciriano, Group Leader at EMBL-EBI. “By training the algorithm directly on long-read sequencing data from cancer samples, we created a new method that can tell the difference between true cancer-related genomic alterations and sequencing artefacts, thereby enabling us to elucidate the mutational processes underlying cancer using long-read sequencing with unprecedented resolution.”

The team’s focus was clear: create a tool sophisticated enough to characterise complex cancer genomes but practical enough for clinical use. SAVANA can accurately distinguish somatic structural variants, copy number aberrations, tumour purity, and ploidy – all key to understanding tumour biology and guiding clinical treatment decisions.

Its rapid analysis and robust error correction make SAVANA well suited for clinical use. The method was recently applied to study osteosarcoma, a rare and aggressive bone cancer that mostly affects young people, where it helped researchers uncover new genomic rearrangements, providing novel insights into how osteosarcoma evolves and progresses.

“The capability to accurately detect structural variants is transformative for clinical diagnostics,” said Adrienne Flanagan, Professor at UCL, Consultant Histopathologist at RNOH. “SAVANA could help us confidently identify genomic alterations relevant for diagnosis and prognosis. Ultimately, this means we would be better placed to deliver personalised treatments for cancer patients.”

The UK is investing significantly in genomic sequencing technologies as part of the NHS Genomic Medicine Service. This initiative aims to improve diagnostic accuracy and support personalised cancer treatments. However, investments in clinical genomics will only achieve their intended impact if genomic data are interpreted accurately.

“Using SAVANA will ensure clinicians receive accurate and reliable genomic data, enabling them to confidently integrate advanced genomic sequencing methods such as long-read sequencing into routine patient care,” said Greg Elgar, Director of Sequencing R&D at Genomics England.

SAVANA is being deployed as part of nationwide initiatives, such as the UK Stratified Medicine Paediatrics project funded by Cancer Research UK and Children With Cancer UK, and co-led by Cortes-Ciriano. This project aims to develop more efficacious and less toxic treatments for childhood cancers using advanced sequencing technologies to better understand tumour biology and monitor disease recurrence.

Additionally, SAVANA is being used in Societal, Ancestry, Molecular and Biological Analyses of Inequalities (SAMBAI), a Cancer Grand Challenges funded project aimed at addressing cancer disparities in recent African heritage populations.

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