Category Archives: Uncategorized

A Leap in Understanding Hypertrophic Cardiomyopathy (Medicine)

Hypertrophic cardiomyopathy (HCM) is the most common of all genetic heart diseases and is the leading cause of sudden cardiac death. HCM is characterized by an abnormal thickening of the heart muscle, which, over time, can lead to cardiac dysfunction and, ultimately, heart failure. 

A paper published June 15 in the Proceedings of the National Academy of Sciences (PNAS) and co-authored by Beth Pruitt, UC Santa Barbara professor of mechanical engineering and director of the UCSB Institute for BioEngineering, describes the results of a complex long-term collaboration that has included researchers at Stanford University, the University of Washington, and the University of Kentucky. The study has led to new understanding of how genetic mutations play out at the cellular level to cause HCM, and new perspectives on how to prevent it.

In the paper, titled “Hypertrophic cardiomyopathy β-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super-relaxed state,” the authors explain that more than one thousand genetic mutations that cause HCM have been identified. The majority of them are found in genes that encode sarcomeric proteins, the structural building blocks of heart muscle responsible for generating and regulating contraction and relaxation. Roughly a third of the mutations are located in β-cardiac myosin, the primary protein that drives contraction of the heart cells.

Contraction of the heart muscle, and every other muscle in our bodies, results from a process in which the motor protein myosin “walks” along a chain of actin molecules, a process known as the cross-bridge cycle. During this process, chemical energy in the form of ATP is converted to mechanical energy, ultimately leading to cardiac contraction. 

Prior to a contraction, the head of one strand of an intertwined two-strand myosin molecule is tucked up against an actin molecule. Muscle contraction is initiated when a molecule of ATP, known as the “energy currency” of biological systems, binds to the myosin head. The myosin head, and the attached ATP, then detaches from the actin, initiating hydrolysis of the ATP, which is transformed into ADP plus a phosphate group. That process releases energy that “cocks” the myosin protein into a high-energy state and changes the shape of the myosin so that it is ready to crawl along the actin. At that point, the phosphate is released from the myosin, causing the myosin to push on the actin and release the phosphate, which leads the myosin to walk to the next chain of actin and contract the muscle. All of this, involving millions of heads of myosin walking across actin in steps that take microseconds to complete, must occur at the proper rate in order to maintain heart health.
Because HCM is often observed in patients having mutations in the β-cardiac myosin protein, it had been hypothesized that HCM mutations cause a cascade of events that manifest, ultimately, in damage to the heart itself. This study put that idea to the test, focusing on a single mutation, P710R, which dramatically decreased in vitro motility velocity — the rate at which the myosin motor walks on actin — in contrast to other MYH7 mutations, which led to increased motility velocity. 

The overarching research question of this project was to learn how a mutation linked to heart disease in patients changes heart function at a cellular level.

The team used CRISPR technology to edit human induced pluripotent derived stem cell cardiomyocytes (cells responsible for heart contraction) by inserting the P710R mutation into them. Pruitt leads the stem cell bank at UCSB, where “clean” cell lines, having no genetic abnormalities, are maintained and reproduced for university researchers. Such clean, mutation-free lines provide a perfect benchmark for comparison with cells to see very precisely the effects of the P710R mutation. For example, the research team is now testing the effects of different mutations linked to heart disease in the same genetic background.

 “You can have ten people with the same gene mutation in this protein, and they can have varying degrees of clinical significance, because the rest of their genome is different; that’s what makes us individuals,” Pruitt says. “These lines let us examine what is a result of the genetic mutation. By comparing the effect of different mutations, we can begin to tease apart how these changes lead to HCM. It allows us to look closely at how and why the cells adapt to the mutation in that way, and to get data and relate it to the thickness of the heart wall and all the other things that happen downstream. 

Nearly fifteen years after the research began while Pruitt was still at Stanford and that led to this collaborative paper, CRISPR technology enables researchers to design cells expressing specific mutations that are linked to cardiac diseases, and then assess molecular and functional changes to determine the cellular impact of individual mutations that have been identified in patients with HCM. These studies will provide a mechanistic understanding of how individual mutations at the molecular level translate to HCM in patients. 

In this project, once the mutation was introduced, the cells were assayed in a collaboration between the Pruitt and Bernstein labs, using traction force microscopy, an assay that allows simultaneous observation of a beating cell and the force it generates. The Spudich led separate studies of the same mutated protein at the molecular level using an optical trap, in which light pressure is applied to control precisely the location and force of an actin “dumbbell” held between beads as myosin heads walk along the actin, to measure myosin’s power cycle. The assay revealed that the P710R mutation reduced the step size of the myosin motor (i.e. the length of each step) and the rate at which the myosin detaches from actin.
In a collaboration with University of Kentucky researcher Kenneth Campbell, these observations were then compared to a computational model of how the myosin motors interact in the cell to generate force. The results confirmed a key role for regulation of what is called myosin’s “super-relaxed state.” As Pruitt explains, “Myosin heads spend a lot of time in a super-relaxed state, referring to when it is unbound from actin. Any mutation or drug that shifts how long or how strongly myosin motors are bound to actin will change the cell force production and change downstream signaling events that drive remodeling and growth or hypertrophy.”

The P710R mutation in this study was found to destabilize the super-relaxed state. As a result, more myosin heads are bound to actin in cells that harbor the mutation, which explains the increase in force that was observed in those cells. 

For Pruitt, a key takeaway from the work, beyond the important scientific findings, is the value of sustained collaboration. “The scales that the paper covers are not typically the subject of research in any one lab or even any two labs,” she says. “That’s why the paper has so many authors, including several students and postdocs working with me, James Spudich, and Daniel Bernstein. 

“It’s significant scientifically but also satisfying in that this level of integration makes it possible to test this idea across multiple scales. It’s been fun to work across these labs and these skills on such an extensive, multidisciplinary collaboration, and to see that the power of molecular measurements and computation, and the cell-derived measurements that allow us to genetically engineer and dissect out a single mutation,” says Pruitt. “This is really phenomenal, to test directly how a particular mutation introduces changes that lead to HCM.”

As a result of this collaboration, Pruitt says, “We can understand what goes on at the cell level. Then we can start to develop models and identify next-generation drug therapies. Instead of just identifying the symptoms, we can look at the mechanisms that underlie the dysfunctions and then address those at the cell level before it turns into a disease.”

Featured image: Professor Beth Pruitt © UC Santa Barbara Engineering

Provided by UC SANTA BARBARA Engineering

Potential New Therapeutic Approach For Chronic Inflammatory Bowel Diseases (Medicine)

FAU research team identify messenger substance protecting cells in the intestine

Why people suffer from chronic inflammatory bowel diseases (IBD) such as ulcerative colitis is only partially understood. However, it is known that the bacteria of the intestinal flora and dysfunction in the immune system play an important role. In patients with IBD, an increased number of cells in the intestinal wall, known as epithelial cells, die. Bacteria then pass from the interior of the intestine into the damaged intestinal wall, causing inflammation and further cell death. The epithelial barrier, the barrier between the intestinal contents and the intestinal wall also becomes more permeable. With increasing cell death, the disease also progresses as more bacteria settle in the damaged intestinal wall – a vicious circle. A research team led by Prof. Dr. Christoph Becker from FAU has now found a mechanism that could prevent cell death, break the vicious circle and potentially be used as a therapy for inflammatory bowel diseases. The results have now been published in the renowned journal Nature Cell Biology.

In mice and tissues of ulcerative colitis patients, researchers found that a messenger substance called prostaglandin E2 can protect epithelial cells from a special form of cell death, necroptosis. Prostaglandins are hormone-like messenger substances that have various effects in the organism. Researchers have found that prostaglandins such as prostaglandin E2 are released in the body during inflammation. However, it is not yet fully understood how prostaglandins regulate inflammatory processes.

In recent years, the researchers have already shown that the incorrect regulation of necroptosis leads to cell death and thus to holes in the intestinal barrier. Prostaglandin E2 prevents this by binding to EP4 receptors on the epithelial cells. The more of these receptors are activated, the fewer cells die, according to the FAU team from the Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology – at Universitätsklinikum Erlangen. Patients with high levels of EP4 on the cell surface show a milder course of disease than patients with low levels of EP4.

The activation of the receptors by prostaglandin E2 thus counteracts the progression of intestinal inflammation. Together with colleagues in Canada, the research team tested an artificially produced molecule that can activate the EP4 receptor, like prostaglandin E2. Treatment with this molecule could prevent excessive cell death in the intestinal barrier and block bacteria from penetrating it. These findings offer a promising new therapy approach for ulcerative colitis and other chronic inflammatory bowel diseases.

Featured image: Microscopic image of a cultured intestinal epithelial cell with cell death programme activated (red). Pores form in the cell membrane (green) causing the cell to die. The nucleus is shown in blue. © FAU

Further information

Patankar, J.V., Müller, T.M., Kantham, S. et al. E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis. Nat Cell Biol 23, 796–807 (2021).

Provided by Friedrich-Alexander-Universität Erlangen-Nürnberg

Why Identical Mutations Cause Different Types Of Cancer? (Medicine)

Why do alterations of certain genes cause cancer only in specific organs of the human body? Scientists at the German Cancer Consortium (DKTK), the Technical University of Munich (TUM), and the University Medical Center Göttingen have now demonstrated that cells originating from different organs are differentially susceptible to activating mutations in cancer drivers: The same mutation in precursor cells of the pancreas or the bile duct leads to fundamental different outcomes. The team discovered for the first time that tissue specific genetic interactions are responsible for the differential susceptibility of the biliary and the pancreatic epithelium towards transformation by oncogenes. The new findings could guide more precise therapeutic decision making in the future.

There have been no major improvements in the treatment of pancreatic and biliary tract cancer in the last decades and no effective targeted therapies are available to date. “The situation for patients with pancreatic and extrahepatic bile duct cancer is still very depressing with approximately only 10% of patients surviving five years,” says Dieter Saur, DKTK Professor for Translational Cancer Research at TUM’s university hospital Klinikum rechts der Isar, DKTK partner site Munich.

DKTK is a consortium centered around the German Cancer Research Center (DKFZ) in Heidelberg, which has long-term collaborative partnerships with specialist oncological centers at universities across Germany.

“To discover novel therapeutic strategies that improve prognosis of these patients, it is essential to understand the fundamental genetic networks and interactions that drive these tumors in a tissue-specific fashion. This will allow highly precise molecular interventions in future.”

The research team looked at the development of biliary tract and pancreatic cancer in mice, replacing the normal “oncogenes” PIK3CA and KRAS with a version containing a mutation identical with that in human cancers. Expression of these oncogenes in the common precursor cells of the extrahepatic bile duct and the pancreas led to very different outcomes. Mice with the mutated PI3K gene developed mostly biliary tract cancer, mice with the mutated KRAS gene instead developed exclusively pancreatic cancer.

This was unexpected because both genes are mutated in both human cancer types. Subsequent analyses discovered the fundamental genetic processes underlying the differential sensitivity of the different tissue types towards oncogenic transformation.

“Our results are an important step toward solving one of the biggest mysteries in oncology: Why do alterations of certain genes cause cancer only in specific organs?” says Chiara Falcomatà the first author of the new publication. “Our studies in mice revealed how genes co-operate to cause cancer in different organs. We identified main players, the order in which they occur during tumor progression, and the molecular processes how they turn normal cells into threatening cancers. Such processes are potential targets for new treatments”.

In the mice, the team uncovered a stepwise process of genetic alterations, which drive the development of these cancer types. Some cooperating genetic events overactivate the PI3K signaling pathway, making them cancerous. Others disrupt regulators proteins, inactivating their ability to suppress cancer progression.

“Understanding the genetic interactions in different cancer types will guide more precise therapeutic decision making in the future” says Günter Schneider, Professor for Translational Cancer Research at the University Medical Center Göttingen. “Our ability to engineer specific genetic alterations in mice allows us to study the function of cancer genes and to model specific cancer subtypes. Such mouse models are also invaluable for testing anticancer drugs before using them in clinical trials”.

“What we showed is that the function of an oncogene is different depending on the tissue type and what other genes are altered,” says Roland Rad Professor at TUM and a DKTK researcher. “These oncogenes need to hijack the intrinsic signaling network of a specific tissue to allow cancer development. Interestingly, such networks exist only in specific tissue types making them susceptible for cancer development.”

These findings have important implications for therapeutic interventions. “The concept that multiple tissue-specific genetic interactions drive cancer progression demonstrates that no single gene can predict responsiveness of a cancer to a particular therapy,” says Saur. “In future, it is key to mechanistically understand the tissue specific determinants of therapeutic response and resistance to get precision medicine to the next level.”

Several of the authors including Dieter Saur and Roland Rad are based at TranslaTUM, TUM’s Center for Translational Cancer Research. In this interdisciplinary research institute, doctors work with colleagues from the fields of natural sciences and engineering on research into causes, diagnostics and potential treatments of cancerous diseases.

Featured image: Pancreatic Cancer, induced by activation of the PIK3CA oncogene © T. Santos/DKTK & TUM

Reference: Chiara Falcomatà, Stefanie Bärthel, Angelika Ulrich, Sandra Diersch, Christian Veltkamp, Lena Rad, Fabio Boniolo, Myriam Solar, Katja Steiger, Barbara Seidler, Magdalena Zukowska, Joanna Madej, Mingsong Wang, Rupert Öllinger, Roman Maresch, Maxim Barenboim, Stefan Eser, Markus Tschurtschenthaler, Arianeb Mehrabi, Stephanie Roessler, Benjamin Goeppert, Alexander Kind, Angelika Schnieke, Maria S. Robles, Allan Bradley, Roland M. Schmid, Marc Schmidt-Supprian, Maximilian Reichert, Wilko Weichert, Owen J. Sansom, Jennifer P. Morton, Roland Rad, Günter Schneider, Dieter Saur: Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer
Cancer Discovery 2021, DOI: 10.1158/2159-8290.CD-21-0209

Provided by DKFZ

NUS Engineers Harvest WiFi Signals to Power Small Electronics (Engineering)

With the rise of the digital age, the amount of WiFi sources to transmit information wirelessly between devices has grown exponentially. This results in the widespread use of the 2.4GHz radio frequency that WiFi uses, with excess signals available to be tapped for alternative uses.

To harness this under-utilised source of energy, a research team from the National University of Singapore (NUS) and Japan’s Tohoku University (TU) has developed a technology that uses tiny smart devices known as spin-torque oscillators (STOs) to harvest and convert wireless radio frequencies into energy to power small electronics. In their study, the researchers had successfully harvested energy using WiFi-band signals to power a light-emitting diode (LED) wirelessly, and without using any battery.

“We are surrounded by WiFi signals, but when we are not using them to access the Internet, they are inactive, and this is a huge waste. Our latest result is a step towards turning readily-available 2.4GHz radio waves into a green source of energy, hence reducing the need for batteries to power electronics that we use regularly. In this way, small electric gadgets and sensors can be powered wirelessly by using radio frequency waves as part of the Internet of Things. With the advent of smart homes and cities, our work could give rise to energy-efficient applications in communication, computing, and neuromorphic systems,” said Professor Yang Hyunsoo from the NUS Department of Electrical and Computer Engineering, who spearheaded the project.

The research was carried out in collaboration with the research team of Professor Guo Yong Xin, who is also from the NUS Department of Electrical and Computer Engineering, as well as Professor Shunsuke Fukami and his team from TU. The results were published in Nature Communications on 18 May 2021.

Converting WiFi signals into usable energy

Spin-torque oscillators are a class of emerging devices that generate microwaves, and have applications in wireless communication systems. However, the application of STOs is hindered due to a low output power and broad linewidth.

A chip embedded with about 50 spin-torque oscillators. © National University of Singapore

While mutual synchronisation of multiple STOs is a way to overcome this problem, current schemes, such as short-range magnetic coupling between multiple STOs, have spatial restrictions. On the other hand, long-range electrical synchronisation using vortex oscillators is limited in frequency responses of only a few hundred MHz. It also requires dedicated current sources for the individual STOs, which can complicate the overall on-chip implementation.

To overcome the spatial and low frequency limitations, the research team came up with an array in which eight STOs are connected in series. Using this array, the 2.4 GHz electromagnetic radio waves that WiFi uses was converted into a direct voltage signal, which was then transmitted to a capacitor to light up a 1.6-volt LED. When the capacitor was charged for five seconds, it was able to light up the same LED for one minute after the wireless power was switched off.

In their study, the researchers also highlighted the importance of electrical topology for designing on-chip STO systems, and compared the series design with the parallel one. They found that the parallel configuration is more useful for wireless transmission due to better time-domain stability, spectral noise behaviour, and control over impedance mismatch. On the other hand, series connections have an advantage for energy harvesting due to the additive effect of the diode-voltage from STOs.

Commenting on the significance of their results, Dr Raghav Sharma, the first author of the paper, shared, “Aside from coming up with an STO array for wireless transmission and energy harvesting, our work also demonstrated control over the synchronising state of coupled STOs using injection locking from an external radio-frequency source. These results are important for prospective applications of synchronised STOs, such as fast-speed neuromorphic computing.”

Next steps

To enhance the energy harvesting ability of their technology, the researchers are looking to increase the number of STOs in the array they had designed. In addition, they are planning to test their energy harvesters for wirelessly charging other useful electronic devices and sensors.

The research team also hopes to work with industry partners to explore the development of on-chip STOs for self-sustained smart systems, which can open up possibilities for wireless charging and wireless signal detection systems.

Featured image: The research breakthrough was achieved by a team led by Professor Yang Hyunsoo (left). Dr Raghav Sharma (right), the first author of the paper, is holding a chip embedded with about 50 spin-torque oscillators. © NUS News

Reference: Sharma, R., Mishra, R., Ngo, T. et al. Electrically connected spin-torque oscillators array for 2.4 GHz WiFi band transmission and energy harvesting. Nat Commun 12, 2924 (2021).

Provided by NUS

‘Flipping’ Optical Wavefront Eliminates Distortions in Multimode Fibers (Engineering)

University of Rochester researchers use vectorial time reversal to demonstrate enhanced channel capacity in a 1-km-long multimode fiber

The use of multimode optical fibers to boost the information capacity of the Internet is severely hampered by distortions that occur during the transmission of images because of a phenomenon called modal crosstalk.

However, University of Rochester researchers at the Institute of Optics have devised a novel technique, described in a paper in Nature Communications, to “flip” the optical wavefront of an image for both polarizations simultaneously, so that it can be transmitted through a multimode fiber without distortion. Researchers at the University of South Florida and at the University of Southern California collaborated on the project.

Lead author Yiyu Zhou, a PhD candidate in the Rochester lab of Robert Boyd, professor of optics, draws an analogy to a multilane highway in describing the challenge the researchers confronted.

“Obviously, a multiple lane highway is faster than a single lane,” Zhou says. “But if a courier is forced to change from lane A to lane B, the package will be delivered to the wrong destination. When this happens in a multimode fiber–when one spatial mode is coupled to another during the propagation through the fiber–it’s what we call modal crosstalk. And we want to suppress that.”

The solution the researchers devised involves digitally pre-shaping the wavefront and polarization of a forward-propagating signal beam to be the phase conjugate of an auxiliary, backward-propagating probe beam–in an experimental realization of vectorial time reversal.

“When an optical beam with perfect wavefronts passes through the multimode fiber, it comes out badly distorted,” explains Boyd, who is also the Canada Excellence Research Chair in Quantum Nonlinear Optics at the University of Ottawa.

“If we use a mirror to send the wavefront back, it will become even more distorted. But if we instead reflect it off a mirror, and also flip the wavefront from front to back, the distortion becomes undone as the waves go back through that distorting medium. In particular, we need perform this procedure for both polarizations simultaneously when the distorting medium is a long multimode fiber.”

The researchers demonstrate that this technology can enhance the channel capacity in a 1-km-long multimode fiber

“Our technique can be used to realize mode-division multiplexing over long, standard multimode fibers to significantly enhance the channel capacity of optical communication links,” Zhou says. “It can potentially be used to increase the Internet speed by one or two orders of magnitude.”

The technique could also be potentially used to improve endoscopy imaging of the brain and other biological tissues, Zhou says.

Other coauthors are Jiapeng Zhao of Boyd’s Rochester lab; Boris Braverman of Boyd’s Ottawa lab; Alexander Fyffe and Zhimin Shi of the University of South Florida, and Runzhou Zhang and Alan Willner of the University of Southern California, Los Angeles.

The research was supported with funding from the U.S. Office of Naval Research; a Banting Postdoctoral Fellowship; the Natural Sciences and Engineering Research Council of Canada; the Canada Research Chairs program; the Canada First Research Excellence Fund; a Vannevar Bush Faculty Fellowship sponsored by the Basic Research Office of the Assistant Secretary of Defense for Research and Engineering; and a Qualcomm Innovation Fellowship.

Featured image: When a well-defined image propagates from the right-hand side to the left-hand side through a 1-km-long multimode fiber, its spatial profile and polarization will be strongly distorted. By flipping the wavefront of the distorted image for both polarizations simultaneously, a technique referred to as vectorial time reversal, an undistorted beam is formed after it passes from left to right through the optical fiber. © Illustration by Yiyu Zhou

Reference: Zhou, Y., Braverman, B., Fyffe, A. et al. High-fidelity spatial mode transmission through a 1-km-long multimode fiber via vectorial time reversal. Nat Commun 12, 1866 (2021).

Provided by University of Rochester

Picture Of the Week: Lone Ranger (Astronomy)

This Picture of the Week appears to show a lone antenna gazing at the sky — but in reality this antenna is far from lonely. It is part of the Atacama Large Millimeter/submillimeter Array (ALMA), a telescope that comprises 66 high-precision antennas spread out across the Chajnantor plateau, located high up in the Chilean Andes. In this image we are treated to a spectacularly multi-coloured view of the sky above ALMA: green airglow hovers above the horizon, the Large Magellanic Cloud peeks out from behind the antenna, and the magnificent sprawl of the Milky Way stretches out overhead. 

These antennas are optimised to collect light at millimetre wavelengths, between infrared and radio waves, giving ALMA a view of the Universe that is very different to our own. Human eyes have evolved to see visible light while ALMA views the cosmos at longer wavelengths, picking up light from some of the coldest objects in the Universe — dense star-forming clouds, discs of debris around newborn stars, distant galaxies, and more. ALMA can probe these objects with unprecedented sensitivity and resolution. The array has observed Einstein Rings, imaged protoplanetarydiscs, and detected complex organic molecules within such discs, suggesting that the Solar System may not be unique in its ability to foster life.


About the Object

Provided by ESO

International Team Identifies Genetic Link Between Face and Brain Shape (Neuroscience)

An interdisciplinary team led by KU Leuven and Stanford has identified 76 overlapping genetic locations that shape both our face and our brain. What the researchers didn’t find is evidence that this genetic overlap also predicts someone’s behavioural-cognitive traits or risk of conditions such as Alzheimer’s disease. This means that the findings help to debunk several persistent pseudoscientific claims about what our face reveals about us.

There were already indications of a genetic link between the shape of our face and that of our brain, says Professor Peter Claes from the Laboratory for Imaging Genetics at KU Leuven, who is the joint senior author of the study with Professor Joanna Wysocka from the Stanford University School of Medicine. “But our knowledge on this link was based on model organism research and clinical knowledge of extremely rare conditions,” Claes continues. “We set out to map the genetic link between individuals’ face and brain shape much more broadly, and for commonly occurring genetic variation in the larger, non-clinical population.”

Brain scans and DNA from the UK Biobank

To study genetic underpinnings of brain shape, the team applied a methodology that Peter Claes and his colleagues had already used in the past to identify genes that determine the shape of our face. Claes: “In these previous studies, we analysed 3D images of faces and linked several data points on these faces to genetic information to find correlations.” This way, the researchers were able to identify various genes that shape our face.

For the current study, the team relied on these previously acquired insights as well as the data available in the UK Biobank, a database from which they used the MRI brain scans and genetic information of 20,000 individuals. Claes: “To be able to analyse the MRI scans, we had to measure the brains shown on the scans. Our specific focus was on variations in the folded external surface of the brain – the typical ‘walnut shape’. We then went on to link the data from the image analyses to the available genetic information. This way, we identified 472 genomic locations that have an impact on the shape of our brain. 351 of these locations have never been reported before. To our surprise, we found that as many as 76 genomic locations predictive of the brain shape had previously already been found to be linked to the face shape. This makes the genetic link between face and brain shape a convincing one.”

The team also found evidence that genetic signals that influence both brain and face shape are enriched in the regions of the genome that regulate gene activity during embryogenesis, either in facial progenitor cells or in the developing brain. This makes sense, Wysocka explains, as the development of the brain and the face are coordinated. “But we did not expect that this developmental cross-talk would be so genetically complex and would have such a broad impact on human variation.”

No genetic link with behaviour or neuropsychiatric disorders

At least as important is what the researchers did not find, says Dr Sahin Naqvi from the Stanford University School of Medicine, who is the first author of this study. “We found a clear genetic link between someone’s face and their brain shape, but this overlap is almost completely unrelated to that individual’s behavioural-cognitive traits.”

Concretely: even with advanced technologies, it is impossible to predict someone’s behaviour based on their facial features. Peter Claes continues: “Our results confirm that there is no genetic evidence for a link between someone’s face and that individual’s behaviour. Therefore, we explicitly dissociate ourselves from pseudoscientific claims to the contrary. For instance, some people claim that they can detect aggressive tendencies in faces by means of artificial intelligence. Not only are such projects completely unethical, they also lack a scientific foundation.”

In their study, the authors also briefly address conditions such as Alzheimer’s, schizophrenia, and bipolar disorder. Claes: “As a starting point, we used the results that were previously published by other teams about the genetic basis of such neuropsychiatric disorders. The possible link with the genes that determine the shape of our face had never been examined before. If you compare existing findings with our new ones, you see a relatively large overlap between the genetic variants that contribute to specific neuropsychiatric disorders and those that play a role in the shape of our brain, but not for those that contribute to our face.” In other words: our risk of developing a neuropsychiatric disorder is not written on our face either.

This research is a collaboration between KU Leuven, Stanford University School of Medicine, University of Pittsburgh, Pennsylvania State University, Indiana University Purdue University Indianapolis, Cardiff University, and George Mason University.

Featured image credit: Public domain

Reference: Naqvi, S., Sleyp, Y., Hoskens, H. et al. Shared heritability of human face and brain shape. Nat Genet (2021).

Provided by KU Leuven

Maternal Exposures to Environmental Chemicals Linked to Autistic-like Behaviours in Children (Medicine)

A new study by Simon Fraser University’s Faculty of Health Sciences researchers – published today in the American Journal of Epidemiology – found correlations between increased expressions of autistic-like behaviours in pre-school aged children to gestational exposure to select environmental toxicants, including metals, pesticides, polychlorinated biphenyls (PCBs), phthalates, and bisphenol-A (BPA).

This population study measured the levels of 25 chemicals in blood and urine samples collected from 1,861 Canadian women during the first trimester of pregnancy. A follow up survey was conducted with 478 participants, using the Social Responsiveness Scale (SRS) tool for assessing autistic-like behaviours in pre- school children.

The researchers found that higher maternal concentrations of cadmium, lead, and some phthalates in blood or urine samples was associated with increased SRS scores, and these associations were particularly strong among children with a higher degree of autistic-like behaviours. Interestingly, the study also noted that increased maternal concentrations of manganese, trans-Nonachlor, many organophosphate pesticide metabolites, and mono-ethyl phthalate (MEP) were most strongly associated with lower SRS scores.

The study’s lead author, Josh Alampi, notes that this study primarily “highlights the relationships between select environmental toxicants and increased SRS scores. Further studies are needed to fully assess the links and impacts of these environmental chemicals on brain development during pregnancy.”

The results were achieved by using a statistical analysis tool, called Bayesian quantile regression, that allowed investigators to determine which individual toxicants were associated with increased SRS scores in a more nuanced way than conventional methods.

“The relationships we discovered between these toxicants and SRS scores would not have been detected through the use of a means-based method of statistical analysis (such as linear regression),” noted Alampi. “Although quantile regression is not frequently used by investigators, it can be a powerful way to analyze complex population-based data.”

Reference: Joshua D Alampi, Bruce P Lanphear, Joseph M Braun, Aimen Chen, Tim K Takaro, Gina Muckle, Tye E Arbuckle, Lawrence C McCandless, Gestational Exposure to Toxicants and Autistic Behaviors using Bayesian Quantile Regression, American Journal of Epidemiology, 2021;, kwab065,

Provided by Simon Fraser University

Origin of Childhood Cancer Malignant Rhabdoid Tumour Discovered (Medicine)

Researchers identified two drugs that could be used to overcome the genetic root of the disease, resuming normal development and bringing hope of new treatments

The first proof of the origin of malignant rhabdoid tumour (MRT), a rare childhood cancer, has been discovered by researchers at the Wellcome Sanger Institute, the Princess Máxima Center for Pediatric Oncology in the Netherlands, and their collaborators.

The study, published today (3 March 2021) in Nature Communications, found that MRT arises from developmental cells in the neural crest* whose maturation is blocked by a genetic defect. The team also identified two drugs that could be used to overcome this block and resume normal development, bringing hope of new treatments for the disease.

Malignant rhabdoid tumour (MRT) is a rare soft tissue cancer that predominantly affects infants. Although these tumours may arise in any part of the body, they usually form in the kidney and the brain. MRT is one of the childhood cancers with the poorest outcomes.

The rarity of MRT, with only 4-5 cases per year in the UK, combined with its aggressiveness, make clinical trials extremely difficult. Until now, the origin of MRT has not been known and no reliably effective treatment currently exists. This new study sought to discover the root of MRT in the hope of identifying new treatments for the disease.

For this study, two cases of MRT were whole genome sequenced at the Wellcome Sanger Institute, alongside corresponding normal tissues. The researchers then conducted phylogenetic analyses of the somatic mutations in the diseased and healthy tissue, in order to ‘reconstruct’ the timeline of normal and abnormal development.

The analyses confirmed that MRT develops from progenitor cells on their way to becoming Schwann cells, a cell type found in the neural crest, due to a mutation in the SMARCB1 gene. This mutation blocks the normal development of these cells, which can then go on to form MRT.

Researchers at the Princess Máxima Center for Pediatric Oncology then inserted the intact SMARCB1 gene into patient-derived MRT organoids**, artificial tumours grown in the laboratory from the patients’ original tumours, to successfully overcome the maturation block that had prevented normal development and led to cancer. Based on single-cell mRNA analyses and predictions made from these experiments, the researchers then identified two existing medicines that overcome the maturation block and could thus be used to treat children with MRT.

“To be able to identify where malignant rhabdoid tumour (MRT) comes from for the first time is an important step in being able to treat this disease, but to confirm that it is possible to overcome the genetic flaw that can cause these tumours is incredibly exciting. The fact that two drugs already exist that we think can be used to treat the disease gives us hope that we can improve outcomes for children diagnosed with MRT.”

Dr Jarno Drost, co-lead author of the study from the Princess Máxima Center for Pediatric Oncology and Oncode Institute

“It is fantastic to see this collaborative research bearing highly translatable outcomes in a childhood cancer with a currently poor prognosis. It emphasises the significant benefit of a National Tumour banking system, that allows collection of rarer tumours and in turn, the best use of such precious tissue through agreement of the CCLG Biological Studies committee that oversees this resource. For this to result in such a meaningful outcome gives new hope to children with malignant rhabdoid tumour (MRT).”

Professor Richard Grundy, Chair of the Children’s Cancer and Leukaemia Group

MRT remains a cancer with very poor outcomes for which few new treatments are on the horizon. This study harnesses cutting edge quantitative and experimental methods, to identify a potential new treatment for MRT.

“We began our enquiry into the origins of malignant rhabdoid tumours in late 2019, so we have gone from hypothesis to discovery of origin to possible treatments for the disease in just over a year. This was possible due to all the leading-edge tools available to us, from organoid technology to single-cell mRNA sequencing to drug screen databases. I hope this study will serve as the blueprint for discovering the origin of other childhood cancers and, ultimately, lead to better outcomes for children affected by these awful diseases.”

Dr Sam Behjati, co-lead author of the study from the Wellcome Sanger Institute


Lars Custers, Eleonora Khabirova and Tim H.H. Coorens et al. (2021). Somatic mutations and single cell transcriptomes reveal the root of malignant rhabdoid tumours. Nature Communications. DOI: 10.1038/s41467-021-21675-6


This research was supported by the Dutch Cancer Society, the European Research Council (ERC), Children Cancer-free foundation (KiKa), the St. Baldrick’s Foundation and Wellcome.

Featured image credit: L. Custers & J. Drost

Provided by Wellcome Sanger Institute