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Developmental Biology

Harmonizing Newborn Genetic Screening: A Data-Driven Approach to Gene Selection

More than a decade ago, researchers launched the BabySeq Project, a pilot program to return newborn genomic sequencing results to parents and measure the effects on newborn care. Today, over 30 international initiatives are exploring the expansion of newborn screening using genomic sequencing (NBSeq), but a new study highlights the substantial variability in gene selection among those programs.

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The world of newborn genetic screening has come a long way since the launch of the BabySeq Project over a decade ago. Today, more than 30 international initiatives are exploring the expansion of this critical public health tool using genomic sequencing (NBSeq). However, a recent study by researchers from Mass General Brigham highlights the substantial variability in gene selection among these programs. In a paper published in Genetics in Medicine, the researchers offer a data-driven approach to prioritizing genes for public health consideration.

“It’s essential that we be thoughtful about which genes and conditions are included in genomic newborn screening programs,” said co-senior author Nina Gold, MD, director of Prenatal Medical Genetics and Metabolism at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “By leveraging machine learning, we can provide a tool that helps policymakers and clinicians make more informed choices, ultimately improving the impact of genomic screening programs.”

The researchers introduced a machine learning model that brings structure and consistency to the selection of genes for NBSeq programs. This is the first publication from the International Consortium of Newborn Sequencing (ICoNS), founded in 2021 by senior author Robert C. Green, MD, MPH, director of the Genomes2People Research Program at Mass General Brigham, and David Bick, MD, PhD, of Genomics England in the United Kingdom.

The study analyzed 4,390 genes included across 27 NBSeq programs, identifying key factors influencing gene inclusion. While the number of genes analyzed by each program ranged from 134 to 4,299, only 74 genes (1.7%) were consistently included in over 80% of programs. The strongest predictors of gene inclusion were whether the condition is on the U.S. Recommended Uniform Screening Panel, has robust natural history data, and if there is strong evidence of treatment efficacy.

Using these insights, the team developed a machine learning model incorporating 13 predictors, achieving high accuracy in predicting gene selection across programs. The model provides a ranked list of genes that can adapt to new evidence and regional needs, enabling more consistent and informed decision-making in NBSeq initiatives worldwide.

“This research represents a significant step toward harmonizing NBSeq programs and ensuring that gene selection reflects the latest scientific evidence and public health priorities,” said Green.

Cell Biology

A 600-Million-Year-Old Body Blueprint Uncovered in Sea Anemones

Sea anemones may hold the key to the ancient origins of body symmetry. A study from the University of Vienna shows they use a molecular mechanism known as BMP shuttling, once thought unique to bilaterally symmetrical animals like humans, insects, and worms. This surprising discovery implies that the blueprint for forming a back-to-belly body axis could date back over 600 million years, to a common ancestor of cnidarians and bilaterians.

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A new study from the University of Vienna has made a groundbreaking discovery in the field of developmental biology. Researchers have found that sea anemones, traditionally considered radially symmetric animals, use a molecular mechanism known as BMP shuttling to pattern their back-to-belly body axis. This finding suggests that bilateral symmetry, which characterizes a vast group of animals including vertebrates, insects, and worms, may have evolved much earlier than previously assumed.

BMP shuttling is a signaling system involving Bone Morphogenetic Proteins (BMPs) and their inhibitor Chordin. In bilaterian animals, this mechanism creates a gradient of BMP activity across the embryo, allowing cells to detect and adopt different fates depending on BMP levels. The study’s findings indicate that sea anemones use BMP shuttling in a similar manner, with cells expressing different fates based on BMP signaling.

To investigate whether sea anemones indeed use BMP shuttling, researchers blocked Chordin production in the embryos of the model sea anemone Nematostella vectensis. Without Chordin, BMP signaling ceased, and the formation of the second body axis failed. However, when Chordin was reintroduced into a small part of the embryo, BMP signaling resumed – but only with a diffusible form of Chordin, which acts as a BMP shuttle.

The presence of BMP shuttling in both cnidarians and bilaterians suggests that this molecular mechanism predates their evolutionary divergence some 600-700 million years ago. The study’s findings open up exciting possibilities for rethinking how body plans evolved in early animals, and may have significant implications for our understanding of the evolution of bilateral symmetry.

The research was supported by the Austrian Science Fund (FWF), grants P32705 and M3291.

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Agriculture and Food

The Hidden Pause: How Bumble Bee Queens Keep Their Colonies Alive

Bumblebee queens don t work nonstop. UC Riverside scientists discovered that queens take strategic reproductive breaks early in colony formation likely to conserve energy and increase the chance of survival. These pauses aren t due to stress but are a built-in response to brood development stages. The study shows queen behavior is far more flexible and dynamic than previously thought, potentially offering new insights into how to protect declining bee populations.

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The world of insects is often shrouded in mystery, but recent research has uncovered a fascinating phenomenon that could hold the key to understanding the survival strategies of bumble bee colonies. A new study from the University of California, Riverside reveals that even the mighty queens, sole founders of their colonies, take regular breaks from reproduction – likely to avoid burning out before their first workers arrive.

In the early stages of colony building, bumblebee queens shoulder the entire workload. They forage for food, incubate their developing brood by heating them with their wing muscles, maintain the nest, and lay eggs. This high-stakes balancing act is crucial, as without the queen, the colony fails. Researchers noticed an intriguing rhythm – a burst of egg-laying followed by several days of apparent inactivity.

The study’s lead author, Blanca Peto, observed this pattern early on while taking daily photos of the nests. “I saw these pauses just by taking daily photos of the nests,” she said. “It wasn’t something I expected. I wanted to know what was happening during those breaks.”

To find out what triggered the pauses, Peto monitored more than 100 queens over a period of 45 days in a controlled insectary. She documented each queen’s nesting activity, closely examining their distinctive clutches – clusters of eggs laid in wax-lined “cups” embedded in pollen mounds. Across the population, a pattern emerged: Many queens paused reproduction for several days, typically after a stretch of intense egg-laying.

The timing of these pauses appeared to align with the developmental stages of the existing brood. To test this, Peto experimentally added broods at different stages – young larvae, older larvae, and pupae – into nests during a queen’s natural pause. The presence of pupae, which are nearly mature bees, prompted queens to resume egg-laying within about 1.5 days. In contrast, without added broods, the pauses stretched to an average of 12.5 days.

This suggests that queens respond to cues from their developing offspring and time their reproductive efforts accordingly. “There’s something about the presence of pupae that signals it’s safe or necessary to start producing again,” Peto said. “It’s a dynamic process, not constant output like we once assumed.”

Eusocial insects, including bumble bees, feature overlapping generations, cooperative brood care, and a division of labor. Conventional thinking about these types of insects is that they’re producing young across all stages of development. However, Peto said this study challenges that conventional thinking about bumble bees, whose reproductive behavior is more nuanced and intermittent.

“What this study showed is that the queen’s reproductive behavior is much more flexible than we thought,” Peto said. “This matters because those early days are incredibly vulnerable. If a queen pushes too hard too fast, the whole colony might not survive.”

The study focused on a single species native to the eastern U.S., but the implications could extend to other bumble bee species or even other eusocial insects. Queens in other species may also pace themselves during solo nest-founding stages. If so, this built-in rhythm could be an evolutionary trait that helps queens survive long enough to raise a workforce.

Multiple bumblebee populations in North America are declining, largely due to habitat loss, pesticide exposure, and climate stress. Understanding the biological needs of queens, the literal foundation of each colony, can help conservationists better protect them.

“Even in a lab where everything is stable and they don’t have to forage, queens still pause,” Peto said. “It tells us this isn’t just a response to stress but something fundamental. They’re managing their energy in a smart way.”

This kind of insight is possible thanks to patient, hands-on observation, something Peto prioritized in her first research project as a graduate student.

“Without queens, there’s no colony. And without colonies, we lose essential pollinators,” Peto said. “These breaks may be the very reason colonies succeed.”

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Biology

Unraveling Microtubule Mysteries: Scientists Crack Code on Cellular Scaffolding Secrets

Scientists found out how naturally unstable filaments decide whether to grow or to shorten.

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A groundbreaking study has shed new light on the fundamental mechanisms governing microtubule growth within cells. Researchers from Queen Mary University of London and the University of Dundee have made a significant breakthrough by discovering that the ability of tubulin proteins at microtubule ends to connect with each other sideways determines whether a microtubule elongates or shortens.

Microtubules are crucial protein structures that form the internal skeleton of cells, providing structural support and generating dynamic forces that push and pull. These tiny filaments constantly assemble and disassemble by adding or removing tubulin building blocks at their ends. However, the precise rules dictating whether a microtubule grows or shrinks have long remained a mystery due to the complexity and miniature size of their ends.

The collaborative research team has cracked part of this code using advanced computer simulations coupled with innovative imaging techniques. This interdisciplinary approach has allowed them to address this complex biological question from a fresh perspective, bridging physics and biology.

Dr. Vladimir Volkov, co-lead author from Queen Mary University of London, explained the significance of their findings: “Understanding how microtubules grow and shorten is very important – this mechanism underlies division and motility of all our cells. Our results will inform future biomedical research, particularly in areas related to cell growth and cancer.”

Dr. Maxim Igaev, co-lead author from the University of Dundee, highlighted the power of their interdisciplinary approach: “Bridging physics and biology has allowed us to address this complex biological question from a fresh perspective. This synergy not only enriches both fields but also paves the way for discoveries that neither discipline could achieve in isolation.”

This exciting research deepens our understanding of fundamental cellular processes and opens potential new avenues for biomedical research, particularly in areas concerning cell proliferation and the development of treatments for diseases like cancer.

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