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Van Andel Institute scientists have pinpointed a key driver of low bone density, a discovery that may lead to improved treatments with fewer side effects for women with osteoporosis.
The findings are described in a study published this month in Science Advances by VAI Associate Professors Connie M. Krawczyk, Ph.D., and Tao Yang, Ph.D.
Their research reveals that loss of an epigenetic modulator, KDM5C, preserves bone mass in mice. KDM5C works by altering epigenetic “marks,” which are akin to “on” and “off” switches that ensure the instructions written in DNA are used at the right time and in the right place.
“Osteoporosis is a common disease that can have debilitating outcomes,” Yang said. “KDM5C is a promising target to treat low bone mass in women because it is highly specific. We’re hopeful that our findings will contribute to improved therapies.”
Nearly 19% of U.S. women aged 50 and older have osteoporosis in their hips and lower spines. Osteoporosis-associated weakening of the bones increases the risk of fractures and poses significant risks to health and quality of life.
Several medications are approved to treat osteoporosis but fears of rare, severe side effects often are a barrier for their use. Treatments that leverage the hormone estrogen also are available, but are only recommended for low-dose, short-term use due in part to associations with cancer risk.
It is well-established that women experience disproportionately lower bone mass than men throughout their lives. Loss of bone mass accelerates with menopause, increasing the risk of osteoporosis and associated fractures for women as they age.
To figure out why this happens, Krawczyk, Yang and their teams looked at the differences in the ways bone is regulated in male and female mice, which share many similarities with humans and are important models for studying health and disease. They focused on specialized cells called osteoclasts, which help maintain bone health by breaking down and recycling old bone.
The researchers found reducing KDM5C disrupted cellular energy production in osteoclasts, which slowed down the recycling process and preserved bone mass. Importantly, KDM5C is linked to X chromosomes, which means it is more active in females than in males.
“Lowering KDM5C levels is like flipping a switch to stop an overactive recycling process. The result is more bone mass, which ultimately means stronger bones,” Krawczyk said. “We’re very excited about this work and look forward to carrying out future studies to refine our findings. At the end of the day, we hope these insights make a difference for people with osteoporosis.”
This study was supported in part by VAI’s Employee Impact Campaign, a philanthropic giving program sustained by VAI employees. This critical funding supports innovative and collaborative projects at the Institute.

The bone density of astronauts — of both the human and rodent variety — decreases in space. Researchers report April 19 in the journal Cell Reports that changes to the gut microbiomes of space travelers might be associated with this bone loss. Rodents that spent a month or more on the International Space Station had altered and more diverse microbiomes, and the bacterial species that bloomed in space may have contributed to the increased production of molecules that are known to influence the bone remodeling process.
“This is just another vivid example showing the dynamic interactions between the microbiome and mammalian hosts. The gut microbiome is constantly monitoring and reacting, and that’s also the case when you’re exposed to microgravity,” says senior author Wenyuan Shi, a microbiologist and chief executive officer at the Forsyth Institute. “We’ve yet to find out whether there’s a causal link between changes to the microbiome and the observed bone loss in microgravity and if it is simply a consequence or an active compensation to mitigate, but the data are encouraging and create new avenues for exploration.”
Our bones aren’t static; even when we’re fully grown, material is constantly being added, removed, and shifted around in a process called bone remodeling. Recent studies have suggested that gut microbes might impact bone remodeling via various mechanisms including interactions with the immune and hormonal systems. Microbes also produce various molecules because of their own metabolism, and some of these metabolites interact indirectly with the cells responsible for bone remodeling.
We’d expect the microbiome to be impacted by space travel for several reasons. “First and foremost, there are the physical forces at play, such as microgravity and cosmic radiation exposure, which affect not only the bacterial cells but also the human cells,” says first author and microbiologist Joseph K. Bedree, who began the work while at UCLA and continued it at the Forsyth Institute. “Likewise, there are numerous resulting effects on host biological systems from microgravity exposure — immune system irregularities, musculoskeletal changes, altered circadian rhythm, stress — and when those systems become imbalanced, the microbial communities potentially could be disrupted, too.”
To explore how the microbiome changes during prolonged exposure to microgravity, and to investigate possible links between these changes and bone density, the researchers sent 20 rodents to the International Space Station. Ten of these rodents returned alive to Earth after 4.5 weeks, and the researchers tracked how their microbiomes recovered upon return. The remaining 10 space rodents remained in orbit for a total of 9 weeks. Twenty “ground control” rodents were housed in identical conditions — although minus the microgravity — on Earth. The team characterized and compared the microbial communities for the different groups over time: before launch off, after return to Earth, and at end of the study. They also evaluated changes in serum metabolites for the space rodents that were exposed to microgravity for the full 9 weeks.
“This is the first time in NASA history that a rodent has been returned to Earth alive,” says Shi. “This meant we were able to gather information about the change in space, and then monitor their microbiome’s recovery when they returned. The good news is that even though the microbiome changes in space, these alterations don’t appear to persist upon returning to Earth.”
When the team characterized and compared the gut microbiomes of the space and ground control rodents, they found that the space rodents had more diverse gut microbiomes. Two types of bacteria — Lactobacillus and Dorea species — were much more abundant in rodents that were exposed microgravity, and their abundance was even higher in rodents that were in space for 9 weeks versus 4.5 weeks. The metabolism of these two bacteria also could have contributed to the elevated metabolites that were detected and associated with microgravity exposure.
“When we mapped the genetic pathways for Lactobacillus and Dorea, they seemed to line up with the metabolites that were elevated during microgravity exposure,” says Bedree. “When someone’s in microgravity and experiencing bone loss, it would make sense that their body would try to compensate and that the biological systems within would be doing that as well, but we need to do more mechanistic studies to truly validate these hypotheses.”
One non-microgravity factor that may have influenced the rodents’ changing microbiome in space is the fact that they were not able to engage in coprophagy, a normal rodent behavior whereby they eat their own feces, which reintroduces microbes back into the gut. However, the rodents that returned from space after 4.5 weeks were able to engage in coprophagy upon return, and this probably contributed to their microbiomes’ recovery.
While this study sheds light on how the microbiome changes during space travel, the authors say that more work needs to be done to understand the possible link between the microbiome and bone density. They plan to continue the research here on Earth.
If we can figure out which microbes support the maintenance of bone density, it could help astronauts stay healthier in space. The researchers say this information could also help people back on Earth who suffer bone loss from non-gravity-related reasons. “This could potentially lead to new tools for managing diseases like osteopenia or osteoporosis, so it’s not just an isolated story in space,” says Shi.

Certain stem cells have a unique ability to move between growth compartments in hair follicles, but get stuck as people age and so lose their ability to mature and maintain hair color, a new study shows.
Led by researchers from NYU Grossman School of Medicine, the new work focused on cells in the skin of mice and also found in humans called melanocyte stem cells, or McSCs. Hair color is controlled by whether nonfunctional but continually multiplying pools of McSCs within hair follicles get the signal to become mature cells that make the protein pigments responsible for color.
Publishing in the journal Nature online April 19, the new study showed that McSCs are remarkably plastic. This means that during normal hair growth, such cells continually move back and forth on the maturity axis as they transit between compartments of the developing hair follicle. It is inside these compartments where McSCs are exposed to different levels of maturity-influencing protein signals.
Specifically, the research team found that McSCs transform between their most primitive stem cell state and the next stage of their maturation, the transit-amplifying state, and depending on their location.
The researchers found that as hair ages, sheds, and then repeatedly grows back, increasing numbers of McSCs get stuck in the stem cell compartment called the hair follicle bulge. There, they remain, do not mature into the transit-amplifying state, and do not travel back to their original location in the germ compartment, where WNT proteins would have prodded them to regenerate into pigment cells.
“Our study adds to our basic understanding of how melanocyte stem cells work to color hair,” said study lead investigator Qi Sun, PhD, a postdoctoral fellow at NYU Langone Health. “The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans. If so, it presents a potential pathway for reversing or preventing the graying of human hair by helping jammed cells to move again between developing hair follicle compartments.”
Researchers say McSC plasticity is not present in other self-regenerating stem cells, such as those making up the hair follicle itself, which are known to move in only one direction along an established timeline as they mature. For example, transit-amplifying hair follicle cells never revert to their original stem cell state. This helps explain in part why hair can keep growing even while its pigmentation fails, says Sun.

Earlier work by the same research team at NYU showed that WNT signaling was needed to stimulate the McSCs to mature and produce pigment. That study had also shown that McSCs were many trillions of times less exposed to WNT signaling in the hair follicle bulge than in the hair germ compartment, which is situated directly below the bulge.
In the latest experiments in mice whose hair was physically aged by plucking and forced regrowth, the number of hair follicles with McSCs lodged in the follicle bulge increased from 15% before plucking to nearly half after forced aging. These cells remained incapable of regenerating or maturing into pigment-producing melanocytes.
The stuck McSCs, the researchers found, ceased their regenerative behavior as they were no longer exposed to much WNT signaling and hence their ability to produce pigment in new hair follicles, which continued to grow.
By contrast, other McSCs that continued to move back and forth between the follicle bulge and hair germ retained their ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire study period of two years.
“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” said study senior investigator Mayumi Ito, PhD, a professor in the Ronald O. Perelman Department of Dermatology and the Department of Cell Biology at NYU Langone Health.

“These findings suggest that melanocyte stem cell motility and reversible differentiation are key to keeping hair healthy and colored,” said Ito, who is also a professor in the Department of Cell Biology at NYU Langone.
Ito says the team has plans to investigate means of restoring motility of McSCs or of physically moving them back to their germ compartment, where they can produce pigment.
For the study, researchers used recent 3D-intravital-imaging and scRNA-seq techniques to track cells in almost real time as they aged and moved within each hair follicle.
Funding for the study was provided by National Institutes of Health grants P30CA016087, S10OD021747, R01AR059768, R01AR074995, and U54CA263001; and Department of Defense grants W81XWH2110435 and W81XWH2110510.
Besides Sun and Ito, other NYU Langone researchers involved in this study are co-investigators Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, Michael Cammer, and Denise Gay. Other study co-investigators are M. Mark Taketo, at Kyoto University in Japan, and Sarah Millar, at Icahn School of Medicine at Mount Sinai in New York City.

Calm body, calm mind, say the practitioners of mindfulness. A new study by researchers at Washington University School of Medicine in St. Louis indicates that the idea that the body and mind are inextricably intertwined is more than just an abstraction. The study shows that parts of the brain area that control movement are plugged into networks involved in thinking and planning, and in control of involuntary bodily functions such as blood pressure and heartbeat. The findings represent a literal linkage of body and mind in the very structure of the brain.
The research, published April 19 in the journal Nature, could help explain some baffling phenomena, such as why anxiety makes some people want to pace back and forth; why stimulating the vagus nerve, which regulates internal organ functions such as digestion and heart rate, may alleviate depression; and why people who exercise regularly report a more positive outlook on life.
“People who meditate say that by calming your body with, say, breathing exercises, you also calm your mind,” said first author Evan M. Gordon, PhD, an assistant professor of radiology at the School of Medicine’s Mallinckrodt Institute of Radiology. “Those sorts of practices can be really helpful for people with anxiety, for example, but so far, there hasn’t been much scientific evidence for how it works. But now we’ve found a connection. We’ve found the place where the highly active, goal-oriented ‘go, go, go’ part of your mind connects to the parts of the brain that control breathing and heart rate. If you calm one down, it absolutely should have feedback effects on the other.”
Gordon and senior author Nico Dosenbach, MD, PhD, an associate professor of neurology, did not set out to answer age-old philosophical questions about the relationship between the body and the mind. They set out to verify the long-established map of the areas of the brain that control movement, using modern brain-imaging techniques.
In the 1930s, neurosurgeon Wilder Penfield, MD, mapped such motor areas of the brain by applying small jolts of electricity to the exposed brains of people undergoing brain surgery, and noting their responses. He discovered that stimulating a narrow strip of tissue on each half of the brain causes specific body parts to twitch. Moreover, the control areas in the brain are arranged in the same order as the body parts they direct, with the toes at one end of each strip and the face at the other. Penfield’s map of the motor regions of the brain — depicted as a homunculus, or “little man” — has become a staple of neuroscience textbooks.
Gordon, Dosenbach and colleagues set about replicating Penfield’s work with functional magnetic resonance imaging (fMRI). They recruited seven healthy adults to undergo hours of fMRI brain scanning while resting or performing tasks. From this high-density dataset, they built individualized brain maps for each participant. Then, they validated their results using three large, publicly available fMRI datasets — the Human Connectome Project, the Adolescent Brain Cognitive Development Study and the UK Biobank — which together contain brain scans from about 50,000 people.

To their surprise, they discovered that Penfield’s map wasn’t quite right. Control of the feet was in the spot Penfield had identified. Same for the hands and the face. But interspersed with those three key areas were another three areas that did not seem to be directly involved in movement at all, even though they lay in the brain’s motor area.
Moreover, the nonmovement areas looked different than the movement areas. They appeared thinner and were strongly connected to each other and to other parts of the brain involved in thinking, planning, mental arousal, pain, and control of internal organs and functions such as blood pressure and heart rate. Further imaging experiments showed that while the nonmovement areas did not become active during movement, they did become active when the person thought about moving.
“All of these connections make sense if you think about what the brain is really for,” Dosenbach said. “The brain is for successfully behaving in the environment so you can achieve your goals without hurting or killing yourself. You move your body for a reason. Of course, the motor areas must be connected to executive function and control of basic bodily processes, like blood pressure and pain. Pain is the most powerful feedback, right? You do something, and it hurts, and you think, ‘I’m not doing that again.'”
Dosenbach and Gordon named their newly identified network the Somato (body)-Cognitive (mind) Action Network, or SCAN. To understand how the network developed and evolved, they scanned the brains of a newborn, a 1-year-old and a 9-year-old. They also analyzed data that had been previously collected on nine monkeys. The network was not detectable in the newborn, but it was clearly evident in the 1-year-old and nearly adult-like in the 9-year-old. The monkeys had a smaller, more rudimentary system without the extensive connections seen in humans.
“This may have started as a simpler system to integrate movement with physiology so that we don’t pass out, for example, when we stand up,” Gordon said. “But as we evolved into organisms that do much more complex thinking and planning, the system has been upgraded to plug in a lot of very complex cognitive elements.”
Clues to the existence of a mind-body network have been around for a long time, scattered in isolated papers and inexplicable observations.
“Penfield was brilliant, and his ideas have been dominant for 90 years, and it created a blind spot in the field,” said Dosenbach, who is also an associate professor of biomedical engineering, of pediatrics, of occupational therapy, of radiology, and of psychological & brain sciences. “Once we started looking for it, we found lots of published data that didn’t quite jibe with his ideas, and alternative interpretations that had been ignored. We pulled together a lot of different data in addition to our own observations, and zoomed out and synthesized it, and came up with a new way of thinking about how the body and the mind are tied together.”

A hitherto unknown mechanism for DNA folding is described in a study in Nature published by researchers from Karolinska Institutet and the Max Planck Institute for Biophysics. Their findings provide new insights into chromosomal processes that are vital to both normal development and to prevent disease.
The DNA in our cells is organised into chromosomes, which are highly dynamic structures that are altered when genes are transcribed, when DNA damage is repaired or when chromosomes are compacte in preparation for cell division. These processes are affected by so called SMC protein complexes (SMC, Structural Maintenance of Chromosomes), which by mediating chromosomal interactions ensure correct spatial organization of the genome.
In humans and other eukaryotes, i.e., organisms whose cells contain a nucleus, there are three such protein complexes. Scientists have already revealed the mechanism of function for two of them. In the present study, the researchers investigated the third, the Smc5/6 complex, the function of which has remained mostly unknown.
“These results reveal the Smc5/6 complex as a new regulator of DNA folding, which can tell us more about how chromosomes are organised,” says Camilla Björkegren, professor at the Department of Cell and Molecular Biology at Karolinska Institutet, who led the study together with Eugene Kim, research group leader at the Max Planck Institute for Biophysics in Frankfurt am Main. “The discovery is also medically relevant, since DNA folding is important for normal chromosome function and for avoiding chromosomal alterations that could lead to disease.”
The researchers have purified the Smc5/6 complex from yeast and, using high-resolution microscopy of individual molecules, have studied how it binds and affects individual DNA molecules. The principles of chromosomal organisation are believed to be generally identical in yeast and humans, which are both eukaryotic organisms. For their experiments, the researchers both protein complex and DNA were labeled with differently coloured fluorescing molecules to make them traceable through a microscope.
Their results show that the Smc5/6 complex operates by extruding an increasingly larger DNA loop, a property it shares with the other known eukaryotic SMC complexes.
The researchers have also examined how the process is regulated and found, amongst other things, that two Smc5/6 complexes are needed to form a loop, while single protein complexes only translocates along the DNA molecule.
Previous research indicates that Smc5/6 inhibits certain viruses and suggests that it also protects against certain types of cancer, and is important to normal fetal development. The KI researchers now want to study how these properties are related to the newly discovered mechanism.
“The next step of our research is to find out how the Smc5/6 complex’s ability to make DNA loops affects their function in cells, which can increase our understanding of how Smc5/6 can function as a virus blocker, protect against cancer and contribute to fetal development,” says Professor Björkegren.
The study was financed by the Swedish Research Council, the Swedish Cancer Society, CIMED (the Centre for Innovative Medicine) and the Max Planck Institute for Biophysics. There are no declared potential conflicts of interest.

Published17 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Michelle RobertsDigital health editorUS scientists believe they may have uncovered why hair turns grey as we age, citing pigment-making cells which lose the ability to mature. The arrested development impacts immature cells which would otherwise have developed into melanocytes which give hair its natural colour or shade. The team from New York University (NYU) studied the process in mice, which have identical cells for fur colour.They say the work could provide a basis for reversing the greying process.According to the British Association of Dermatologists (BAD), work on melanocytes might also help our understanding and treatment of certain cancers and other medical conditions too.How does hair turn grey?We grow and shed hair all the time – it’s a normal cycle that happens throughout life. New hair grows from hair follicles, found in the skin, where the pigment-producing melanocytes also reside. Melanocytes continuously decay and renew too. New ones are made from stem cells and it’s these cells that the researchers believe become “stuck” in limbo in people whose hair has turned grey. NYU Langone Health team used special scans and lab techniques to study the cell-ageing process. As hair ages, sheds and then repeatedly grows back, increasing numbers of the melanocyte stem cells become sluggish at their job. The stem cells stop roaming around the follicle and become fixed, thereby failing to mature into fully-fledged melanocytes. With no pigment being produced, the hair turns grey, white or silver.”Our study adds to our basic understanding of how melanocyte stem cells work to colour hair,” study lead investigator Dr Qi Sun, a post-doctoral fellow at NYU Langone Health, told Nature journal.”The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans. If so, it presents a potential pathway for reversing or preventing the greying.”The women choosing to love their natural grey hairWhy stress turns hair whiteIt is not the first time scientists have suggested that greying hair might be a partially reversible process. Poor nutrition is one possible, treatable cause of premature greying.Some researchers claim stress might contribute to human hair turning white, and have suggested removing anxiety might restore the pigmentation process – at least for a while. Other research suggests genetics, or our DNA, partly determines when we go grey. Image source, Getty ImagesWhile some prefer to hide grey hair with dye, others embrace it. Some even choose to get ahead of nature, and prematurely colour hair silver, white or grey. According to Glamour Magazine, silver hair is “the spring hair colour trend that the cool girls are rocking”. “We’ve spotted one shade, in particular, taking off. Oyster grey is the fresh, breezy, pearlescent colour trend that’s cropping up all over Instagram,” the article says. One hairstylist, Luke Hersheson, recently told British Vogue: “At one point it was a big no-no to have grey hair, but now we don’t equate grey hair with being ‘old’ – so many people are doing it.”Post-lockdown, there is a feeling of liberty – many got into a grey hair rut because they couldn’t see their colourists, but came out of the other side and actually enjoyed the change.”Experts advise against plucking out ‘rogue’ grey hairs. It won’t stop the next one that grows from the same follicle from being grey. If you damage the hair follicle, it may be hard for new hair to grow, meaning you could be left with less hair or even bald patches.Dr Leila Asfour from the British Association of Dermatologists told the BBC work on hair colour was big business: “The global hair colour market is projected to attain a value of $33.7bn by 2030. Clearly there’s a demand. “The obvious implication of this research, when it comes to the general public, is that it means being one step closer to finding a way to reverse our grey hairs. “But this study’s results help the medical field understand better other conditions where these stem cells may have a role – for example, understand the underlying nature of the deadliest skin cancer we treat called melanoma.”It might help with a medical condition called alopecia areata too, where the immune system attacks the hair and causes it to fall out. Sometimes the hair grows back white in these patients, she explained. And it could give more clues about vitiligo – a skin condition where patients develop white skin patches. Scientists have tried surgically placing hair follicles in the affected areas to help regenerate the colour from the pigment found in the hair follicle. “More research is needed,” Dr Asfour says. Dr Yusur Al-Nuaimi from the British Hair and Nail Society said scalp health was important for supporting good head hair growth, especially as we age. “The recent study in mice adds to our understanding of the hair follicle and how the pigment-producing cells function. We are already discovering more about the potential of stem cell therapies for conditions including hair loss and studies such as this one, with new findings about the colour-producing cells, may lead to an array of future treatment options for our patients.”More on this storyScientists discover ‘why stress turns hair white’22 January 2020Grey hair gene discovered by scientists1 March 2016’My mum found my first grey hair at seven’19 July 2018Related Internet LinksNYU Langone HealthNature journalBritish Association of DermatologistsThe BBC is not responsible for the content of external sites.

A preconception and early-pregnancy diet that contains lots of fruit, vegetables, seafood, dairy, eggs and grain may be associated with reducing risk of miscarriage, a new review of research suggests.
Researchers at the University of Birmingham, funded by Tommy’s, analysed 20 studies which explored women and birthing people’s eating habits in the months before and shortly after conceiving a baby to see whether these studies showed evidence of association with a lower or higher chance of miscarriage.
Writing in the journal Fertility and Sterility the Tommy’s National Centre for Miscarriage Research team conclude that there is evidence to suggest a diet rich in fruit, vegetables, seafood, dairy products, eggs and grain reduces miscarriage risk.
These are foods which typically make up ‘healthy’ well-balanced diets, with previous evidence showing that eating a well-rounded diet which is rich in vitamins and minerals during pregnancy is important.
The research review found that, when compared to low consumption, high intake of fruit may be associated with a 61% reduction in miscarriage risk. High vegetable intake may be associated with a 41% reduction in miscarriage risk. For dairy products it is a 37% reduction, 33% for grains, 19% for seafood and eggs.
Led by Dr Yealin Chung, researchers also looked at whether pre-defined dietary types, such as the Mediterranean Diet or Fertility Diet could also be linked to miscarriage risk. They could not find evidence that following any of these diets lowered or raised risk.

However, a whole diet containing healthy foods overall, or foods rich in antioxidant sources, and low in pro-inflammatory foods or unhealthy food groups may be associated with a reduction in miscarriage risk for women.
A diet high in processed food was shown to be associated with doubling of miscarriage risk.
The studies included in the analysis focused on the peri-conception period — a period before and during the first 3 months of pregnancy. Data collected from a total of 63,838 healthy women of reproductive age was included, with information on their diets typically collected through food frequency questionnaires for each study.
Dr Chung explains:
“Miscarriage is common, with estimates suggesting 1 in 6 pregnancies end in miscarriage, and there are many known causes, from problems with the baby’s chromosomes to infections in the womb.

“Yet nearly 50% of early pregnancy losses remain unexplained and in the absence of a cause, parents often turn to their healthcare providers for guidance on the best ways to be as healthy as possible and reduce the risk of future miscarriages.
“There’s a growing body of evidence to show that lifestyle changes — including changes to diet, stopping smoking and not drinking alcohol — before conceiving and in your pregnancy’s early stages — may have an impact.
“We strongly encourage couples to consider the importance of making positive lifestyle choices when planning for a family, and to continue with these healthy choices throughout their pregnancy and beyond. By knowing that positive lifestyle choices can make a significant difference in reducing the risk of miscarriage, couples can feel empowered to take charge of their health and the health of their baby.”
Tommy’s midwife Juliette Ward says:
“Advice on diet is one of the most-discussed subjects for us when talking with pregnant women and birthing people. We know that baby loss is very rarely the result of someone’s lifestyle choices, but many people want to know how to be as healthy as possible in pregnancy. Following a healthy diet, taking supplements like Vitamin D and folic acid, exercise and trying to lower stress are all things people can try to do, but there’s been a lack of clear evidence on the links between diet choices and miscarriage.
“Given this lack of evidence, there aren’t any evidence-based guidelines outlining dietary advice for women and birthing people or their partners — something the findings of this review suggest could make a real impact in helping people reduce their risk.”
More studies are needed, the Tommy’s team conclude, particularly research which looks at whether a food group or diet and its link to miscarriage risk is causal, and research which could accurately estimate how effective a change in diet could be in the critical stages of conception and pregnancy.

Small interfering RNAs (siRNAs) are novel therapeutics that can be used to treat a wide range of diseases. This has led to a growing demand for selective, efficient, and safe ways of delivering siRNA in cells. Now, in a cooperation between the Universities of Amsterdam and Leiden, researchers have developed dedicated molecular nanocages for siRNA delivery. In a paper just out in the Journal Chem they present nanocages that are easy to prepare and display tuneable siRNA delivery characteristics.
The nanocages were developed in the research group for Homogeneous, Supramolecular and Bio-inspired catalysis of Prof. Joost Reek and Bas de Bruin at the University of Amsterdam’s Van ‘t Hoff Institute for Molecular Sciences, and further studies in the group Prof. Alexander Kros at the Leiden Institute of Chemistry. The researchers were motivated by the potential of siRNA in gene therapy, which requires the need for effective delivery systems. They set out to develop nanocages with functional groups at the outside, making the cages capable of binding siRNA strands. As the binding is based on reversible bonds, the siRNA can in principle be released in a cellular environment. To explore the delivery characteristics of their nanocages, the researchers performed a laboratory study using various human cancer cells.
A range of nanocages
The nanocages are constructions of small molecular building blocks, so-called ditopic ligands, that are connected using metal atoms. A typical cage consists of 12 metal atoms and 24 ligands, hence the abbreviation M12L24. The researchers designed and synthesized five different ligands to form molecular cages with different siRNA binding affinities. They then prepared a range of siRNA binding nanocages using platinum or palladium as connecting metal. The palladium nanocages are less stable in a cellular environment, and decomposition is one of the siRNA releasing mechanisms.
After screening nanocage characteristics such as stability and siRNA binding capability, the delivery characteristics were put to the test in assays based on siRNA-mediated Green Fluorescent Protein (GFP) silencing. The cages were used to deliver siRNA to human GFP-expressing cells, so that fluorescence measurements could establish successful siRNA delivery. Two types of human cell lines were used: HeLa and U2Os.
Cage composition determines siRNA delivery
To their surprise, the researchers could not only demonstrate satisfying siRNA delivery, but also discovered a remarkable differentiation depending on the metal used in the nanocage. Where a platinum-based Pt12L24 nanocage showed highly effective siRNA delivery to U2OS cells, it showed little efficiency for HeLa. By contrast, the palladium-based Pd12L24 nanocage, derived from the same ligand building block, delivered siRNA to HeLa but not to U2OS. Such differentiation could not be observed in experiments were a commercially applied delivery system (lipofectamine) was used. The M12L24 nanocages thus introduce the possibility of tuning siRNA delivery characteristics by tuning the nanocage composition.
In their Chem paper, the researchers consider this unique cell selectivity feature of the nanoparticles a promising addition to the field of targeted RNA gene material delivery, whose full potential is yet to be uncovered. Even though the current results were obtained in highly controlled laboratory research, they expect that the tuneable RNA delivery of their nanocages will spawn future developments of highly desirable selective RNA nanomedicines.

Over a hundred years after the discovery of the neuron by neuroanatomist Santiago Ramón y Cajal, scientists continue to deepen their knowledge of the brain and its development. In a publication in Science Advances on April 5, a team from the Institut Pasteur and the CNRS, in collaboration with Harvard University, revealed novel insights into how cells in the outer layers of the brain interact immediately after birth during formation of the cerebellum, the brain region towards the back of the skull. The scientists demonstrated a novel type of connection between neural precursor cells via nanotubes, even before the formation of synapses, the conventional junctions between neurons.
In 2009, Chiara Zurzolo’s team (Membrane Traffic and Pathogenesis Unit at the Institut Pasteur) identified a novel mechanism for direct communication between neuronal cells in culture via nanoscopic tunnels, known as tunneling nanotubes. These are involved in the spread of various toxic proteins that accumulate in the brain during neurodegenerative diseases. Nanotubes may therefore be a suitable target for the treatment of these diseases or cancers, where they are also present.
In this new study, the researchers discovered nanoscopic tunnels that connect precursor cells in the brain, more specifically the cerebellum — an area that develops after birth and is important for making postural adjustments to maintain balance — as they mature into neurons. These tunnels, although similar in size, vary in shape from one to another: some contain branches while others don’t, some are enveloped by the cells they connect while others are exposed to their local environment. The authors believe these intercellular connections (ICs) may enable the exchange of molecules that help pre-neuronal cells physically migrate across various layers and reach their final destination as the brain develops.
Intriguingly, ICs share anatomical similarities with bridges formed when cells finish dividing. “ICs could derive from cellular division but persist during cell migration, so this study could shed light on the mechanisms allowing coordination between cell division and migration implicated in brain development. On the other hand, ICs established between cells post mitotically could allow direct exchange between cells beyond the usual synaptic connections, representing a revolution in our understanding of brain connectivity. We show that there are not only synapses allowing communication between cells in the brain, there are also nanotubes,” says Dr. Zurzolo, senior author and head of the Membrane Traffic and Pathogenesis Unit (Institut Pasteur/CNRS).
To achieve these discoveries, the researchers used a three-dimensional (3D) electron microscopy method and brain cells from mouse models to study how the brain regions communicate between each other. Very high resolution neural network maps could thus be reconstructed. The 3D cerebellum volume produced and used for the study contains over 2,000 cells. “If you really want to understand how cells behave in a three-dimensional environment, and map the location and distribution of these tunnels, you have to reconstruct an entire ecosystem of the brain, which requires extraordinary effort with twenty or so people involved over 4 years,” said the article’s first author Diego Cordero.
To meet the challenges of working with the wide range of cell types the brain contains, the authors used an AI tool to automatically distinguish cortical layers. Furthermore, they developed an open-source program called CellWalker to characterize morphological features of 3D segments. The tissue block was reconstructed from brain section images. This program being made freely available will enable scientists to quickly and easily analyze the complex anatomical information embedded in these types of microscope images.
The next step will be to identify the biological function of these cellular tunnels to understand their role in the development of the central nervous system and in other brain regions, and their function in communication between brain cells in neurodegenerative diseases and cancers.The computational tools developed will be made available to other research teams around the globe.

Plants that glow under ultraviolet (UV) light aren’t only a figment of science fiction TV and movies. Roots of a traditional medicine plant called the orange climber, or Toddalia asiatica, can fluoresce an ethereal blue hue. And now, researchers in ACS Central Science have identified two coumarin molecules that could be responsible. These natural coumarins have unique fluorescent properties, and one of the compounds could someday be used for medical imaging.
Fluorescent substances take in UV light that’s directed on them and release vibrantly colored visible light. And some glow even more brightly when they are close together, a phenomenon seen in compounds called aggregation-induced emission luminogens (AIEgens). They are key components in some optical devices, cellular imaging techniques and environmental sensors. However, these molecules are usually made in a lab, and many are toxic. Some plants already have this ability, so, Ben Zhong Tang, Zheng Zhao, Xiao-Dong Luo and colleagues turned to nature to find naturally occurring and safer AIEgens.
The researchers dried orange climber roots, crushed them into a powder, and then isolated and identified coumarin compounds with aggregation-induced emission properties: 5-methoxyseselin (5-MOS) and 6-methoxyseselin (6-MOS). When dissolved in an organic solvent, 5-MOS exhibited a blue-green glow and 6-MOS had a slightly dimmer blue glow. In addition, both AIEgens had low cytotoxicity and good biocompatibility. Then in a final series of experiments, the team found that mitochondria could be clearly identified in live cells stained with 5-MOS without any additional processing, making cell imaging easier and faster than with most current methods. The newly reported compound is a natural, plant-derived option that could advance bioimaging, the researchers say.