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Birth Defects

Pregnancy Triggers Lasting Changes to the Mouse Intestine

Researchers have found that the small intestine grows in response to pregnancy in mice. This partially irreversible change may help mice support a pregnancy and prepare for a second.

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The Francis Crick Institute has made a groundbreaking discovery: the small intestine grows in response to pregnancy in mice. This irreversible change may help mice support a pregnancy and prepare for a second. The research team, led by Irene Miguel-Aliaga, found that pregnant mice had a longer small intestine from just seven days into the pregnancy. By the end of the pregnancy, around day 18, the small intestine was 18% longer.

Interestingly, the small intestine remained longer after birth, even up to 35 days after the mice had finished lactating. This suggests that the change isn’t reversible and might be a trade-off in energy. The team observed that the small intestine was even longer after a second pregnancy than the first.

Inside the small intestine, the villi (protrusions that absorb nutrients) and crypts (where the cells supplying the villi are produced) became longer and deeper at the same time as the gut lengthened. However, both returned to pre-pregnancy values just seven days after weaning.

The researchers altered the diet of the mice, including probiotic intake, to show that these physiological changes in pregnancy occurred regardless of nutritional change. They then took a deeper dive into what was happening in the villi.

They found that precursors of intestinal epithelial cells were rapidly growing in number and newly generated cells migrated faster up the villi in early pregnancy. These effects continued after birth into lactation but returned to pre-pregnancy rates just seven days after weaning.

By looking at which genes were switched on during pregnancy, the researchers saw the biggest number of genetic changes in enterocytes, nutrient-absorbing cells in the villi that are produced by precursor cells in the crypt. These changes were largely related to increasing metabolic activity.

One of the metabolic effects observed at a very early stage was an increase in a membrane protein called SGLT3a. Unlike other SGLT proteins, SGLT3a does not sense glucose levels outside of the cell but responds to sodium and protons instead. An increase in SGLT3a was responsible for about 45% of the villi growth triggered by reproduction, including cell expansion, but wasn’t necessary for entire small intestine lengthening.

The team believes that hormones triggered by reproduction may play a role in switching on the gene for SGLT3a, as pseudo-pregnant mice – females whose pregnancy hormone levels have increased after mating with sterile males – still showed some villi growth and intestinal lengthening.

Irene Miguel-Aliaga said: “We don’t often think about organs changing size or appearance in response to triggers in adulthood rather than earlier childhood and adolescent development, but the gut is a striking example of how the body responds to a new challenge at different stages of life, in this case pregnancy.”

Tomotsune Ameku, former postdoctoral researcher at the Crick, now Assistant Professor at Science Tokyo and first author of the study, said: “Understanding how pregnancy impacts the body in other mammals is a critical first step to understanding this in people. We don’t fully understand why the gut expands in response to pregnancy, but we think it must give an evolutionary advantage and help mice reproduce regularly.”

The researchers are now investigating whether other cell types in the mouse intestine also experience remodelling during pregnancy, and whether this happens in humans, by looking at gut length in people who have and haven’t had children.

Autism

CRISPR-edited stem cells hold key to understanding autism spectrum disorder

A team at Kobe University has created a game-changing resource for autism research: 63 mouse embryonic stem cell lines, each carrying a genetic mutation strongly associated with the disorder. By pairing classic stem cell manipulation with precise CRISPR gene editing, they ve built a standardized platform that mirrors autism-linked genetic conditions in mice. These models not only replicate autism-related traits but also expose key dysfunctions, like the brain s inability to clean up faulty proteins.

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CRISPR technology has revolutionized genetics research, enabling scientists to edit genes with unprecedented precision. Recently, researchers at Kobe University developed a new method for modifying embryonic stem cells using CRISPR, creating a bank of 63 mouse embryonic stem cell lines containing the mutations most strongly associated with autism spectrum disorder (ASD). This breakthrough achievement has shed light on the hidden causes of ASD.

For decades, scientists have known that genetics play a significant role in the development of ASD. However, pinpointing the precise cause and mechanism remained elusive due to the lack of a standardized biological model for studying the effects of different mutations associated with the disorder. To address this challenge, Takumi Toru and his team at Kobe University embarked on a journey to create a reliable model by combining conventional manipulation techniques for mouse embryonic stem cells with CRISPR gene editing.

The new method proved highly efficient in making genetic variants of these cells, allowing the researchers to produce 63 mouse embryonic stem cell lines containing the mutations most strongly associated with ASD. These cell lines were further developed into various cell types and tissues, even generating adult mice with their genetic variations. The analysis of these cell lines revealed that autism-causing mutations often result in neurons being unable to eliminate misshapen proteins.

This finding is particularly interesting since the local production of proteins is a unique feature in neurons, and a lack of quality control of these proteins may be a causal factor of neuronal defects in ASD. Takumi expects that this achievement will be an invaluable resource for researchers studying autism and searching for drug targets. Moreover, the genetic variants studied are also implicated in other neuropsychiatric disorders such as schizophrenia and bipolar disorder, making this library potentially useful for studying these conditions as well.

This research was funded by various organizations, including the Japan Society for the Promotion of Science and the National Center of Neurology and Psychiatry. The study demonstrates the potential of CRISPR technology to reveal the hidden causes of complex diseases like ASD, paving the way for future discoveries and treatments.

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Back and Neck Pain

Unveiling the Secrets of the Universe: The Largest-ever Map Reveals 10x More Early Galaxies Than Expected

An international team of scientists has unveiled the largest and most detailed map of the universe ever created using the James Webb Space Telescope, revealing nearly 800,000 galaxies stretching back to almost the beginning of time. The COSMOS-Web project not only challenges long-held beliefs about galaxy formation in the early universe but also unexpectedly revealed 10 times more galaxies than anticipated along with supermassive black holes Hubble couldn t see.

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The COSMOS-Web field, a vast map of the universe, has been released to the public, and it’s a game-changer. The largest-ever map of the cosmos, built with data collected by the James Webb Space Telescope (JWST), consists of imaging and a catalog of nearly 800,000 galaxies spanning nearly all of cosmic time.

The goal of the COSMOS-Web collaboration was to create this deep field of space on a physical scale that far exceeded anything that had been done before. “If you had a printout of the Hubble Ultra Deep Field on a standard piece of paper,” said UC Santa Barbara physics professor Caitlin Casey, “our image would be slightly larger than a 13-foot by 13-foot-wide mural, at the same depth.” That’s what we’re looking at here – a cosmic neighborhood that’s truly breathtaking.

The COSMOS-Web composite image reaches back about 13.5 billion years, covering about 98% of all cosmic time. The researchers wanted to see not just some of the most interesting galaxies at the beginning of time but also to get a wider view of cosmic environments that existed during the early universe, when the first stars, galaxies, and black holes formed.

And what a big surprise it turned out to be! Before JWST turned on, Casey said they made their best predictions about how many more galaxies the space telescope would see. But the best measurements from Hubble suggested that galaxies within the first 500 million years would be incredibly rare. “It makes sense,” she explained – “the Big Bang happens and things take time to gravitationally collapse and form, and for stars to turn on.”

But with JWST, they see roughly 10 times more galaxies than expected at these incredible distances. And it’s not just seeing more; they’re also seeing different types of galaxies and black holes that were previously invisible.

While the COSMOS-Web images and catalog answer many questions astronomers have had about the early universe, they also spark more questions. “Since the telescope turned on we’ve been wondering ‘Are these JWST datasets breaking the cosmological model?'” Casey said. “Because the universe was producing too much light too early; it had only about 400 million years to form something like a billion solar masses of stars.”

In releasing the data to the public, the hope is that other astronomers from all over the world will use it to further refine our understanding of how the early universe was populated and how everything evolved to the present day. The dataset may also provide clues to other outstanding mysteries of the cosmos, such as dark matter and physics of the early universe that may be different from what we know today.

“A big part of this project is the democratization of science and making tools and data from the best telescopes accessible to the broader community,” Casey said. The data was made public almost immediately after it was gathered, but only in its raw form, useful only to those with specialized technical knowledge and supercomputer access to process and interpret it.

The COSMOS collaboration has worked tirelessly for the past two years to convert raw data into broadly usable images and catalogs. In creating these products and releasing them, the researchers hope that even undergraduate astronomers could dig into the material and learn something new.

“Because the best science is really done when everyone thinks about the same data set differently,” Casey said. “It’s not just for one group of people to figure out the mysteries.”

For the COSMOS collaboration, the exploration continues. They’ve headed back to the deep field to further map and study it. “We have more data collection coming up,” she said. “We think we have identified the earliest galaxies in the image, but we need to verify that.”

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Autism

The Elusive Science of Tickling: Unraveling the Mysteries of a 2000-Year-Old Enigma

How come you can’t tickle yourself? And why can some people handle tickling perfectly fine while others scream their heads off? Neuroscientists argue that we should take tickle research more seriously.

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The science of tickling has been shrouded in mystery for over 2000 years, leaving even the great philosophers Socrates and Charles Darwin baffled. Despite its ubiquity in human interaction, from playful teasing between parents and children to social bonding and emotional expression, the intricacies of tickling remain poorly understood. Neuroscientist Konstantina Kilteni argues that it’s time to take tickle research seriously, shedding light on the complex interplay of motor, social, neurological, developmental, and evolutionary aspects involved.

One of the most intriguing questions surrounding tickling is why we can’t tickle ourselves. Our brain appears to distinguish between self-induced and external stimuli, effectively “switching off” the tickling reflex when we know exactly where and when we’ll be tickled. This phenomenon has sparked interest in understanding what happens in our brain when we’re subjected to ticklish sensations.

Research suggests that people with autism spectrum disorder (ASD) perceive touches as more ticklish than those without ASD, offering a unique window into differences in brain development and function between individuals with and without the condition. Investigating this difference could provide valuable insights into the neurobiology of ASD and potentially inform strategies for better understanding and supporting individuals on the autism spectrum.

From an evolutionary perspective, the purpose and significance of tickling remain unclear. Kilteni notes that even apes like bonobos and gorillas exhibit responses to ticklish touches, while rats have been observed displaying similar behaviors. These observations raise questions about the role of tickling in human evolution and development, as well as its potential functions in social bonding and emotional expression.

To tackle these questions, Kilteni has established a specialized lab dedicated to studying tickling, where researchers can control and replicate various types of ticklish stimuli using mechanical devices like the “tickling chair.” By meticulously recording brain activity and physical reactions such as heart rate, sweating, breathing, laughter, and screaming responses, scientists hope to unlock the secrets of tickling and shed light on its significance in human biology and behavior.

As research continues to unravel the mysteries of tickling, it’s clear that this seemingly simple phenomenon holds a wealth of complexity and intrigue. By taking tickle research seriously, scientists like Kilteni aim to reveal new insights into human brain development, social bonding, emotional expression, and even the intricacies of ASD. The journey ahead promises to be fascinating, as we continue to explore the elusive science of tickling.

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