Culture

Based on genome-wide experiments, the human body has 2,064 genes relevant to COVID-19. So why are researchers only studying 611 of them?

A historical bias -- which has long dictated which human genes are studied -- is now affecting how biomedical researchers study COVID-19, according to new Northwestern University research.

Although biomedical researchers know that many overlooked human genes play a role in COVID-19, they currently do not study them. Instead, researchers that study COVID-19 continue to focus on human genes that have already been heavily investigated independent of coronaviruses.

"For understandable reasons, researchers tend to build upon existing knowledge and research tools. They appear to select genes to study based on the ease of experimentation rather than their ultimate relevance to a disease," said Northwestern's Thomas Stoeger, who co-led the research. "This means that research into COVID-19 concentrates only on a small subset of the human genes involved in the response to the virus. Consequently, many aspects of the response of human cells toward COVID-19 remain not understood."

"There are many genes related to COVID-19, but we don't know what they are doing in the context of COVID-19," added Northwestern's Luís Amaral, who co-led the study with Stoeger. "We didn't study these genes before the pandemic, and COVID-19 does not seem to be an incentive to investigate them."

The research will be published on Nov. 24 in the journal eLife.

Stoeger is a data science scholar at the Northwestern Institute on Complex Systems (NICO) and the Center for Genetic Medicine. Through a "Pathway to Independence" award from the National Institute of Aging, Stoeger is starting a research laboratory dedicated to uncovering unstudied genes with important contributions to aging and age-related diseases. Amaral is the Erastus O. Haven Professor of Chemical and Biological Engineering in Northwestern's McCormick School of Engineering. Stoeger and Amaral are both members of Successful Clinical Response in Pneumonia Therapy (SCRIPT) Systems Biology Center.

Pinpointing a historical bias

This study builds on Stoeger and Amaral's 2018 research, which was the first to explain why some human genes are more popular to study than others. In that work, they found that 30% of all genes have never been studied and less than 20% of genes are the subject of more than 90% of published papers.

Despite the increasing availability of new techniques to study and characterize genes, researchers continue to study a small group of genes that scientists have studied since the 1980s. Historically, these genes have been easier to investigate experimentally. If an animal model has a similar gene to humans, for example, researchers are more likely to study that gene. The Northwestern team also discovered that postdoctoral fellows and Ph.D. students who focus on poorly characterized genes have a 50% reduced chance of becoming an independent researcher.

Although the Human Genome Project -- the identification and mapping of all human genes, completed in 2003 -- aimed to expand the scope of scientific study beyond this small subset of genes, it has yet to fulfill this aim.

"The bias to study the exact same human genes is very high," Amaral said. "The entire system is fighting the very purpose of the agencies and scientific knowledge, which is to broaden the set of things we study and understand. We need to make a concerted effort to incentivize the study of other genes important to human health."

Bias continues into COVID-era

For the new study, Stoeger and Amaral turned to LitCOVID, a collection of research publications related to COVID-19, curated by the National Library of Medicine. LitCOVID tags genes mentioned in the titles, abstracts or results sections of individual publications.

Northwestern researchers analyzed 10,395 published papers and pre-prints from the collection. Then, they integrated them into a custom database along with more than 100 different biological and bibliometric databases in an effort to survey and measure all aspects of biomedical research. Finally, they compared genes mentioned in the COVID-19 papers to COVID-19-related genes as identified by four genome-wide studies.

Stoeger and Amaral also tracked the occurrence of genes appearing in COVID-19 literature over time. Surprisingly, they observed that studies of COVID-19 genes are becoming not more but less expansive since the onset of the pandemic.

The team hopes its study inspires other researchers to be aware of past biases and to explore unstudied genes.

"Our findings have a direct implication on the long-term planning of scientific policymakers," Stoeger said. "We can point researchers toward human genes that are important for the cellular response against viruses but risk being ignored due to historically acquired biases, which are culturally reinforced."

If you open your office door one morning and there is a new package waiting on your desk, that's what you will notice most in the otherwise unchanged room. A new study by MIT and Boston University neuroscientists finds that the dynamic interplay of different brain wave frequencies, rather than dedicated circuitry, appears to govern the brain's knack for highlighting what's surprising and downplaying what's predictable.

By measuring thousands of neurons along the surface, or cortex, of the brain in animals as they reacted to predictable and surprising images, the researchers observed that low frequency alpha and beta brain waves, or rhythms, originating in the brain's frontal cognitive regions tamped down neural activity associated with predictable stimuli. That paved the way for neurons in sensory regions in the back of the brain to push forward information associated with unexpected stimuli via higher-frequency gamma waves. The backflow of alpha/beta carrying inhibitory predictions typically channeled through deeper layers of the cortex, while the forward flow of excitatory gamma carrying novel stimuli propagated across superficial layers.

"These interactions between beta and gamma are happening all over the cortex," said Earl Miller, Picower Professor of Neuroscience in the Department of Brain and Cognitive Sciences at MIT and co-senior author of the study in Proceedings of the National Academy of Sciences. "And it's not generic - it targets the processing of specific stimuli."

In those regards, this new study extends much of Miller's recent work. Previously his lab at The Picower Institute for Learning and Memory has shown that in the prefrontal cortex, working memory depends on bursts of beta rhythms from deep layers regulating gamma frequency activity in more superficial layers. Those findings built, in part, on research published in 2012 by postdoc André Bastos, who is lead author of the new paper. Now the new study and another published by Miller's lab earlier this year suggest that this push and pull between the frequency bands is a common regulatory system of information flow in the cortex. Moreover, the new results show experimentally that it has a key role in predictive coding (as Bastos began to theorize in 2012), not just the related function of working memory.

Predictive coding is a key cognitive function that appears to become disrupted in autism spectrum disorders, noted Miller and Bastos. Some people with autism struggle to regard familiar stimuli as such, treating everything as new and equally salient. That can interfere with learning to recognize predictable situations and therefore the ability to make generalizations about experience.

"Because you are not able to tamp down and actively regulate predicted information, the brain is in a constant state of surging information forward which can be overwhelming," Bastos said. In fact, for anyone, he added, being in a completely new place where predictions of the environment have not yet had time to form can produce a feeling of sensory overload.

Setting and violating expectations

In the study, the team gave animals a simplified predictive coding experience. They were presented with an image as a cue, and then after a brief pause three images returned to the screen including the original. The animals simply had to direct their gaze to the previously cued image to complete the task. Sometimes the cue would be the same for many trials on end (thereby becoming predictable and familiar). Sometimes the cue would suddenly change, violating the predicted expectation. As animals played the game, the scientists were reading out neural activity and overall rhythms produced by that activity in five areas across the cortex, from visual areas in the back of the head to a parietal cortex in the middle, to cognitive cortices, including the prefrontal cortex, in the front.

The team wasn't looking to analyze working memory, or how the animals held the cue image in memory. Instead they were measuring differences made when the cue image was predictable vs. when it was not. Their measurements showed that unpredicted stimuli generated more neural activity than predictable ones. They also revealed that the activity associated with unpredicted stimuli was strongest in the gamma frequency band (and the very low frequency theta band), while activity associated with predicted stimuli was strongest in alpha/beta frequencies.

These changes in power in each frequency weren't across the board - it was greatest specifically among neurons that responded most to the presented stimulus. That means that the regulatory changes of brain waves were acting most strongly on the neural circuitry processing the cue images the animals were seeing. For this reason, the team refers to their conceptual model of predictive coding as "predictive routing."

"Our paper shows that predictive coding can work without specialized circuits for detecting mismatches between predictions and reality," Miller said.

Bastos further explained, "The key element of this new model is that prediction can be accomplished by selectively inhibiting routes of information flow that carry predictable information."

Co-senior author Nancy Kopell, William Fairfield Warren Distinguished Professor of Mathematics at Boston University, added, "To be able to support that idea required the elaborate experiments described in the paper, involving measurements from multiple parts of the brain."

Subsequent analysis of the data also showed other key trends. Among them was that the coherence of activity between cortical regions was stronger in the alpha/beta band when the cue image was predictable and stronger in gamma when it was not. Moreover, the direction of these different bands (how they propagated back and forth across the cortex) showed that alpha/beta fed back from higher cognitive) regions to lower (sensory) regions, while gamma fed forward from lower regions to higher ones.

Paying attention to exceptions

The scientists also saw that alpha/beta mostly peaked in deeper layers of the visual cortices, while gamma often was strongest in superficial layers. But there were exceptions along the way. The parietal cortex region 7A bucked the trend of peaking in gamma for unexpected stimuli, instead peaking in the higher end of the beta frequency band. One possibility, Kopell says, is that 7A was involved in a working memory buffer, which is believed to use beta oscillations. Another explanation could be that 7A's beta activity is related not to prediction as much as attention. Animals performing the task did need to pay at least some degree of attention to the cue, whether it was predictable or not.

Designing experiments that can fully separate attention from prediction could be an important future direction, Bastos said. Another important future goal will be to create computational models that simulate the interactions between layers and frequencies to inhibit predicted information.

"The laminar detail from the current data set will be very useful in producing such a model," Kopell said.

A team from the Institut national de la recherche scientifique (INRS) has demonstrated the effectiveness of an inexpensive molecule to fight antibiotic-resistant strains of the bacteria responsible for gonorrhea and meningococcal meningitis. These two infections affect millions of people worldwide. The results of this research, led by Professor Frédéric Veyrier and Professor Annie Castonguay, have just been published online in the Antimicrobial Agents and Chemotherapy journal.

Antibiotic Resistance

In recent years, rising rates of antibiotic resistance have been of concern to the World Health Organization (WHO), who has celebrated the World Antimicrobial Awareness Week, from November 18th to 24th 2020. This concern is particularly true in the case of Neisseria gonorrhoeae, for which some strains have developed resistance to all effective antibiotics. This bacterium is responsible for gonorrhea, an infection whose incidence has almost tripled in the last decade in Canada. Resistant strains of Neisseria meningitidis, which cause bacterial meningitis, have also emerged. In the current pandemic context, scientists are particularly concerned about a rise in antibiotic resistance due to their increased use.

Unlike other bacteria, Neisseria that cause meningitis and gonorrhea evolve very rapidly because of certain intrinsic properties. For example, they have a great capacity to acquire genes from other bacteria. They also have a suboptimal DNA repair system that leads to mutations; antibiotic resistance can therefore easily emerge. The fact that these diseases affect many people around the world also gives them many opportunities to evolve, explaining why it is urgent to develop new ways to fight these bacteria.

A Specific Molecule

The research team has demonstrated the efficacy of a simple molecule in bacterial cultures and in a model of infection. Well known by chemists, this molecule is accessible, inexpensive, and could greatly help in the fight against these two types of pathogenic Neisseria. The advantage of this molecule is its specificity: "We noticed that the molecule only affects pathogenic Neisseria. It does not affect other types of Neisseria that are found in the upper respiratory system and can be beneficial," underlines Professor Frédéric Veyrier, also the scientific manager of the Platform for Characterization of Biological and Synthetic Nanovehicles.

During its experiments, the research team tested whether there was any possible resistance to the molecule: "We were able to isolate strains of bacteria that were less sensitive to the treatment, but this resistance was a double-edged sword because these mutants completely lost their virulence" says the microbiologist.

For the moment, the team does not know exactly why the molecule reacts specifically with the two types of Neisseria, but they suspect a connection with the membrane of these pathogens. This specificity opens the door to more fundamental research to determine what makes one bacterium virulent compared to others.

The next step will be to modify the structure of the molecule to make it more efficient, while maintaining its specificity. In parallel, the team wishes to identify an industrial partner to evaluate the possibility of developing a potential treatment.

A Nanyang Technological University, Singapore (NTU Singapore) study has found that some Singaporeans have reported that, despite being aware of the existence of 'deepfakes' in general, they believe they have circulated deepfake content on social media which they later found out was a hoax.

Deepfakes, a portmanteau of 'deep learning' and 'fake', are ultrarealistic fake videos made with artificial intelligence (AI) software to depict people doing things they have never done - not just slowing them down or changing the pitch of their voice, but also making them appear to say things that they have never said at all.

In a survey of 1,231 Singaporeans led by NTU Singapore's Assistant Professor Saifuddin Ahmed, 54 per cent of the respondents said they were aware of deepfakes, of which one in three reported sharing content on social media that they subsequently learnt was a deepfake.

The study also found that more than one in five of those who are aware of deepfakes said that they regularly encounter deepfakes online.

The survey findings, reported in the journal Telematics and Informatics in October, come in the wake of rising numbers of deepfake videos identified online. Over the six months to June 2020, Sensity, a deepfake detection technology firm , estimates that identified deepfake videos online had doubled to 49,081.

Deepfakes that have gone viral include one with former President Barack Obama using an expletive to describe President Donald Trump in 2018, and another last year of Facebook founder Mark Zuckerberg claiming to control the future, thanks to stolen data.

Assistant Professor Saifuddin of NTU's Wee Kim Wee School of Communication and Information said: "Fake news refers to false information published under the guise of being authentic news to mislead people, and deepfakes are a new, far more insidious form of fake news. In some countries, we are already witnessing how such deepfakes can be used to create non-consensual porn, incite fear and violence, and influence civic mistrust. As the AI technology behind the creation of deepfakes evolves, it will be even more challenging to discern fact from fiction."

"While tech companies like Facebook, Twitter and Google have started to label what they have identified as manipulated online content like deepfakes, more efforts will be required to educate the citizenry in effectively negating such content."

Americans more likely than Singaporeans to share deepfakes

The study benchmarked the findings on Singaporeans' understanding of deepfakes against a similar demographic and number of respondents in the United States.

Respondents in the US were more aware of deepfakes (61% in US vs. 54% in SG). They said they were also more concerned by and frequently exposed to deepfakes. More people reported sharing content that they later learnt was a deepfake in the US than in Singapore (39% in US vs. 33% in SG).

Asst Prof Saifuddin said: "These differences are not surprising, given the more widespread relevance and public discussion surrounding deepfakes in the US. More recently, a rise in the number of deepfakes, including those of President Donald Trump, has raised anxieties regarding the destructive potential of this form of disinformation.

"On the other hand, Singapore has not witnessed direct impacts of deepfakes, and the government has introduced the Protection from Online Falsehoods and Manipulation Act (POFMA) to limit the threat posed by disinformation, including deepfakes."

But legislation alone is not enough, he added, citing a 2018 survey by global independent market research agency Ipsos which found that while four in five Singaporeans say that they can confidently spot fake news, more than 90 per cent mistakenly identified at least one in five fake headlines as being real.

"The government's legislation to inhibit the pervasive threat of disinformation has also been helpful, but we need to continue improving digital media literacy going forward, especially for those who are less capable of discerning facts from disinformation," said Asst Prof Saifuddin, whose research interests include social media and public opinion.

The NTU study on deepfake awareness was funded by the University and Singapore's Ministry of Education, and the findings are part of a longer-term study that examines citizens' trust in AI technology.

Scientists at Sanford Burnham Prebys Medical Discovery Institute have created a drug that can lure stem cells to damaged tissue and improve treatment efficacy--a scientific first and a major advance for the field of regenerative medicine. The discovery, published in the Proceedings of the National Academy of Sciences (PNAS), could improve current stem cell therapies designed to treat neurological disorders such as spinal cord injury, stroke, amyotrophic lateral sclerosis?(ALS) and other neurodegenerative disorders; and expand their use to new conditions, such as heart disease or arthritis.

Toxic cells (green) disappeared when mice with a neurodegenerative condition received both therapeutic stem cells (red) and the drug SDV1a-which corresponded with longer lives and delayed symptom onset. These results suggest that SDV1a can be used to improve the efficacy of stem cell treatments.

"The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine," says Evan Y. Snyder, M.D. Ph.D., professor and director of the Center for Stem Cells & Regenerative Medicine at Sanford Burnham Prebys and senior author of the study. "Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact."

Nearly 15 years ago, Snyder and his team discovered that stem cells are drawn to inflammation--a biological "fire alarm" that signals damage has occurred. However, using inflammation as a therapeutic lure isn't feasible because an inflammatory environment can be harmful to the body. Thus, scientists have been on the hunt for tools to help stem cells migrate--or "home"--to desired places in the body. This tool would be helpful for disorders in which initial inflammatory signals fade over time--such as chronic spinal cord injury or stroke--and conditions where the role of inflammation is not clearly understood, such as heart disease.

"Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease," says Maria T. Millan, M.D., president and CEO of the California Institute for Regenerative Medicine (CIRM), which partially funded the research. "Dr. Snyder's group has identified a drug that could boost the ability of neural stem cells to home to sites of injury and initiate repair. This candidate could help speed the development of stem cell treatments for conditions such as spinal cord injury and Alzheimer's disease."

A drug with only the "good bits"

In the study, the scientists modified CXCL12--an inflammatory molecule that Snyder's team previously discovered could guide healing stem cells to sites in need of repair--to create a drug called SDV1a. The new drug works by enhancing stem cell binding and minimizing inflammatory signaling--and can be injected anywhere to lure stem cells to a specific location without causing inflammation.

"Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit," says Snyder. "Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation."

To demonstrate that the new drug is able to improve the efficacy of a stem cell treatment, the researchers implanted SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. This experiment showed that SDV1a helped the human neural stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than the mice that didn't receive the drug. Importantly, inflammation was not activated, and the stem cells were able to suppress any pre-existing inflammation.

Next steps

The researchers have already begun testing SDV1a's ability to improve stem cell therapy in a mouse model of ALS, also known as Lou Gehrig's disease, which is caused by a progressive loss of motor neurons in the brain. Previous studies conducted by Snyder's team indicated that broadening the spread of neural stem cells helps more motor neurons survive--so the scientists are hopeful that the strategic placement of SDV1a will expand the terrain covered by neuroprotective stem cells and help slow the onset and progression of the disease.

"We are optimistic that this drug's mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer," says Snyder. "Interestingly, because CXCL12 and its receptor [JK1] are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well."

What if we didn't have skin? We would have no sense of touch, no detection of coldness or pain, leaving us inept to respond to any situation. The skin is not just a protective shell for organs, but rather a signaling system for survival that provides information on the external stimuli or temperature, or a meteorological observatory that reports the weather. Tactile receptors, tightly packed throughout the skin, feel the temperature or mechanical stimuli - such as touching or pinching - and convert them into electrical signals to the brain.

The challenge for electronic skin, being developed for use in artificial skins or humanlike robots like the humanoids, is to make it feel the temperatures and movements like how human skin feels them as much as possible. So far, there are electronic skins that can detect movement or temperature separately, but none are able to recognize both simultaneously like the human skin.

A joint research team consisting of POSTECH professor Unyong Jeong and Dr. Insang You of the Department of Materials Science and Engineering, and Professor Zhenan Bao of Stanford University have together developed the multimodal ion-electronic skin that can measure the temperature and mechanical stimulation at the same time. The research findings, published on November 20th edition of Science, are characterized by making very simple structures through applying special properties of the ion conductors.

There are various tactile receptors in the human skin that can detect hot or cold temperatures as well as other tactile sensations such as pinching, twisting or pushing. Through these receptors, humans can distinguish between the mechanical stimuli and temperature. The conventional electronic skin fabricated so far had the issue of having large errors in measuring temperature if mechanical stimuli were applied to the skin.

Human skin is freely stretchable yet unbreakable because it is full of electrolytes, so the joint research team made the sensor using them. They also took advantage of the fact that the ion conductor material containing electrolyte can have different measurable properties according to its measurement frequency. On the basis of the new finding, a multifunctional artificial receptor was created that can measure a tactile sensation and temperature at the same time.

In addition, the research team derived variables - the charge relaxation time and the normalized capacitance - that only respond to temperatures in ion conductors and variables that only respond to mechanical stimuli. The outputs of the variables could be obtained measuring at only two measurement frequencies. The charge relaxation time, which is the time it takes for the polarization of the ions to disappear, can measure temperature and does not respond to movements, and the normalized capacitance can measure the movements without responding to temperature.

This artificial receptor with a simple electrode-electrolyte-electrode structure has great commercialization potential and accurately measures the temperature of the object applied as well as the direction or strain profile upon external stimuli such as squeezing, pinching, spreading and twisting.

The multimodal ion-electronic skin, which can be freely stretched or modified but can also detect temperature, is anticipated to be applicable in wearable temperature sensors or in robot skins for humanlike robots like humanoids.

"When an index finger touches an electronic skin, the electronic skin detects contact as a temperature change, and when a finger pushes the skin, the back part of the contact area stretches and recognizes it as movement," explained Dr. Insang You of POSTECH who is the first author of the paper. "I suspect that this mechanism is one of the ways that the actual human skin recognizes different stimuli like temperature and movement."

"This study is the first step in opening the door for multimodal electronic skin research using electrolytes," remarked Professor Unyong Jeong of POSTECH and the corresponding author. "The ultimate goal of this research is to create artificial ion-electronic skin that simulates human tactile receptors and neurotransmitters, which will help restore the sense of touch in patients who have lost their tactile sensation due to illness or accidents."

Understanding how particles travel through a device is vital for improving the efficiency of solar cells. Researchers from KAUST, working with an international team of scientists, have now developed a set of design guidelines for enhancing the performance of molecular materials.

When a packet of light, or photon, is absorbed by a semiconductor, it generates a pair of particles known as an exciton. An electron is one part of this pair; the other is its positively charged equivalent, called a hole. Excitons are electrically neutral, so it is impossible to set them in motion by applying an electric field. Instead the excitons "hop" by a random motion or diffusion. The dissociation of the excitons into charges is necessary to create a current but is highly improbable in an organic semiconductor.

"So typically, we need to blend two semiconductors, a so-called electron donor and an electron acceptor, to efficiently generate free charges," explains Yuliar Firdaus. "The donor and acceptor materials penetrate into one another; maximizing the exciton diffusion length-- the distance the exciton can travel before recombining and being lost-- is crucial for optimizing the organic solar cell's performance.

Many previous organic solar cells were made by blending a polymer with molecules, known as fullerenes. But more recently, replacing the fullerene with other organic materials such as nonfullerene small molecules produced impressive improvements in device efficiency.

Firdaus and colleagues combined measurements of the photocurrent with ultrafast spectroscopy to calculate the diffusion length of a wide variety of nonfullerene molecules. They observed very long exciton diffusion lengths, in the range of 20 to 47 nanometers--an improvement on the 5 to 10 nanometer range characteristic of fullerenes.

To better understand this improvement, the team compared data describing the crystallographic structure of the molecules with quantum chemical calculations. In this way they could identify key relationships between the chemical structure of the molecule and the diffusion length. With these connections established, the scientists developed a set of rules to aid in the synthesis of improved materials and, ultimately, help the design of organic photovoltaic devices with improved conversion efficiency.

"Next, we plan to investigate how film processing processes might affect the exciton transfer rate of the existing small-molecule acceptors," says Firdaus. "We are also interested in translating the molecular design rules to synthesize new acceptor materials with better performance."

Tsukuba, Japan - Researchers from the Faculty of Health and Sport Sciences at the University of Tsukuba studied the way blind players and sighted non-athletes tracked an incoming noise-making ball. They found that blind players employed a larger downward head rotation when trapping the rolling ball, compared with blindfolded sighted volunteers. This work may help explain the methods visually impaired people utilize to complete daily tasks, as well as assist in the creation of new smart-assistant devices.

Blind soccer is a sport that can be enjoyed by anyone, regardless of visual ability. Except for the goalkeepers, players are blindfolded during the game, and can follow the location of the ball using the sounds it emits. To better understand the way visually impaired players are able to receive and control the ball, scientists at the University of Tsukuba recruited both experienced blind soccer players as well as sighted nonathlete volunteers. A system of ten cameras was used to keep track of the three-dimensional position of the reflective markers attached to the body of each test subject. The task for each participant was to trap an incoming rolling ball with his right foot while blindfolded.

The seasoned blind footballers showed a larger downward head rotation angle, as well as better overall performance, compared with the sighted non-athletes. However, no significant differences were found in the horizontal head or trunk rotation. This indicates that blind footballers can more closely match the motion of their head with the movement of the approaching ball.

"Our study suggests that blind footballers are better at keeping the ball in a consistent egocentric direction relative to the head throughout the trapping process," Senior author Professor Masahiro Kokubu says.

It is known that blind individuals can have superior hearing compared with sighted individuals, especially for sound localization. "Our results are consistent with previous findings that practice improves the ability to track sounds even in blind individuals who already do better than sighted people on this task," explains Professor Kokubu. These results also suggest that the strategy of blind footballers to accurately localize a ball is similar to the way high-level baseball batters rotate their heads. The results of this project may lead to improved smart devices that take advantage of these same techniques to assist visually impaired individuals.

CINCINNATI - Physicians and scientists at Cincinnati Children's Hospital Medical Center used new stem cell technology to regenerate and study living patient-specific skin in the lab, giving them a precise close up view of how inherited DNA defects cause skin damage and deadly squamous cell carcinoma in children and young adults with Fanconi anemia (FA).

Reporting their findings in the journal Cell Stem Cell, the researchers are now using the complex 3D laboratory models of FA patient epidermis - and the enhanced biological detail they provide - to screen for drugs that could slow or stop the disease progression. Study authors explain that new human stem cell-derived tissue models overcome inherent limitations when studying human disease in mice, giving researchers an innovative tool to finally solve what has been a long-standing and dangerous molecular mystery.

"Squamous cell carcinoma is a global health problem, and DNA instability in children with Fanconi anemia makes them extremely susceptible," said Susanne Wells, PhD, the study's principal investigator and a cancer biologist at the Cincinnati Children's Cancer and Blood Diseases Institute. "Unlike the general population, squamous cell carcinomas that arise in the head, neck, anogenital regions, and skin of children and young adults with FA tend to be unusually aggressive and deadly."

Treatments are available for FA, but Wells explained that they come with side effects because of how the disease works.

"We need effective treatments, but identifying the molecular and cellular consequences of FA gene mutations has been difficult because mouse models don't fully recapitulate human disease. Fortunately, our bioengineered models of 3D human epidermis are helping us overcome this," said Wells, who is also director of the Epithelial Carcinogenesis and Stem Cell Program.

A Pathway to DNA Instability

FA is an inherited disorder caused by loss of function mutations in over 20 genes in human reproductive (germline) cells. Usually, the FA pathway plays an important role in normal skin structure and function. And although all cells contain crosslinked DNA, defective DNA repair machinery in people with FA causes the accumulation of defective crosslinks. This makes kids with FA prone to DNA instability, bone marrow failure, and cancer.

Researchers on the current study demonstrate this important role in their most recent data. They conducted a small controlled clinical test to demonstrate that patients with FA mutations are more prone to skin damage and blistering from environmental stress. The test, approved by the Cincinnati Children's Institutional Review Board, involved applying moderate pressure to the arms of children and young adults with FA and to a control group without FA.

Individuals with FA developed skin blisters much faster when compared to individuals in the non-FA control group, suggesting intrinsic skin fragility in this population.

Mimicking Nature's Developmental Process

To track the biological development of epidermal vulnerabilities in children with FA, donated skin tissue was used to generate patient-derived pluripotent stem cells (PSCs). The PSCs take on embryonic-like traits and can form any kind of tissue in the body. The patient-specific stem cells in this study harbored FA gene mutations, which for the purpose of direct comparison could be corrected by researchers using an inducible system.

The PSCs were then biochemically converted into epidermal stem and progenitor cells, the developmental stage at which FA mutations usually begin to disrupt skin function. Epidermal stem and progenitor cells were then used to generate complex 3D epidermal models called organotypic skin rafts, which also harbored FA mutations when left uncorrected.

The FA patient-specific tissues had diminished cell-to-cell junctions, key biological connections important to skin formation and function, together with other molecular and structural defects. These defects translated into accelerated blistering of skin after mechanically induced stress, which sets off disease processes that can progress into cancer. Skin fragility in FA might also promote cancer via elevated exposure of the body to carcinogens in the external environment.

According to the study's first author, Sonya Ruiz-Torres, PhD, a fellow in the Wells laboratory, the researchers are continuing their project. Because the study was limited by a small number of patients, the researchers are generating 3D human organotypic skin rafts to study a broader range of people with FA mutations. This should give scientists a more comprehensive look at different FA gene mutation disease processes, understand how these promote squamous cell carcinoma, and help advance the potential clinical impact of their work.

Special activity trackers can be used to fairly accurately determine the respiratory rate of people while they sleep. This is the result of a new study conducted by researchers at Martin Luther University Halle-Wittenberg (MLU) together with Charité - Universitätsmedizin Berlin and published in the journal Scientific Reports. In the future, activity trackers could be used to detect the early stages of a disease, as a person's respiratory rate can indicate signs of an undetected medical problem.

Breathing tells a lot about a patient's health. Several studies have shown that deviations from a normal respiratory rate, which is about 12 to 18 times a minute, can be an indication of a serious illness. Breathing less than six times a minute is a stronger indication of a life-threatening issue than an abnormal heartbeat. Conversely, very rapid breathing can be an early sign of heart problems. "Nevertheless, the relevance of respiratory rates in the early detection of medical risks has garnered little attention," says Dr Jan Kantelhardt, a physicist at MLU. For several years now, his research group has been investigating how physical data from measuring devices can improve patient diagnostics.

To date, a reliable measurement of respiratory rates over longer periods of time is only possible in clinics that have the right equipment. However, health studies with several hundred thousand participants, for example, require simpler devices. Up to now, a standard electrocardiogram (ECG) has often been used to measure heart rates and rhythms, thus allowing conclusions to be drawn about breathing. "We were looking for a new, inexpensive way to measure respiration," says Kantelhardt.

Together with the research group led by Professor Thomas Penzel from the Interdisciplinary Center of Sleep Medicine at the Charité, the team from Halle wanted to examine whether special activity trackers could provide a reliable alternative to ECGs. Staff members in the sleep laboratory at the Charité placed a wristband, in addition to the usual equipment, on around 400 patients. The wristbands registered movement and also took a simple ECG measurement via an electrode attached to the skin. "They are like fitness trackers but much more precise. We can use our own software to analyse the raw data," says Kantelhardt. This enables the researchers to detect the slightest bit of movement - even if the patient's arm turns slightly when breathing while asleep.

A comparison of the data from the sleep laboratory showed that these minimal movements allow more precise conclusions to be drawn about the respiratory rate than the ECG recorded at the same time. "If there is too much movement, breathing can no longer be measured with the armbands. But there are always periods at night where we can very reliably observe breathing," says Kantelhardt. According to the researcher, the armbands could be used, for example, as a diagnostic tool before a patient is sent to a sleep laboratory.

The new method will initially be used to evaluate some of the data from the so-called GNC Health Study, which began in 2014. As part of the long-term nationwide study, approximately 200,000 people regularly undergo medical examinations and interviews about their living conditions and medical histories. Some of the participants also received the same activity trackers as those in the current study. The overall aim of the project is to better understand the development of common diseases such as cancer, diabetes or cardiac arrhythmia in order to improve preventative measures, early diagnosis, and treatment in Germany.

Researchers from King's College London have identified the brain activity for the first time in a newborn baby when they are learning an association between different types of sensory experiences. Using advanced MRI scanning techniques and robotics, the researchers found that a baby's brain activity can be changed through these associations, shedding new light on the possibility of rehabilitating babies with injured brains and promoting the development of life-long skills such as speech, language and movement.

Published recently in Cerebral Cortex, the researcher builds on the fact that learning associations is a very important part of babies' development but the activity inside the brain that was responsible for learning these associations was unknown and unstudied.

Lead researcher, Dr Tomoki Arichi said it is the first time it has been shown that babies' brain activity can be altered through associative learning - and in particular, brain responses become associated with particular stimuli, in this case, sound.

"We also found that when a baby is learning, it actually is activating lots of different parts of the brain, so it is starting to incorporate the 'wider network' inside the brain which is important for processing activity," he said.

A total of 24 infants were studied by playing them a sound of a jingling bell for six seconds, coupled with a gentle movement induced by a custom-made 3D printed robot strapped to their right hand.

During this time, the resulting brain activity was measured using functional MRI (fMRI). After 20 minutes of learning an association between the two types of stimuli, the babies then just heard the sound on its own and the resulting brain activity was compared to that seen before the period of learning.

Dr Arichi said not only do the results provide new information about what is happening inside the normal baby brain when it is learning, but also have implications for the injured brain.

If a baby was not capable of processing movement, or movement is not associated with normal activity inside the brain (such might be the case in a baby with cerebral palsy), clinicians could then be able to induce that activity by learning an association with sound, and using the sound simulation to try and amplify and rehabilitate their movement.

"With our findings it raises the possibility of trying to do something to help with that through targeted stimulation and learning associations," Dr Arichi said.

"It is possible to induce activity inside the part of the brain that normally processes movement, for instance, just by using a single sound. This could be used in conjunction with rehabilitation or to try and help guide brain development early in life."

When babies are born, they have a new sensory experience around them that is completely different to what they would have been experiencing inside the womb.

They must then start to quickly understand their environment and the relationships between different things happening, which is even more important in babies that have injuries to their brain.

The researchers sought to understand how babies start to learn these key relationships between different kinds of sensory experiences and how this then contributes to the early stages of overall brain development.

"A baby's brain is constantly learning associations and changing its activity all the time so that it can respond to the new experiences that are around it," Dr Arichi said.

"In terms of influencing patients and interpreting it in a wider context, what it means is that we should be thinking about how we could help with disorders of brain development from a very early stage in life because we know that experience is constantly shaping the newborn brain's activity."

Two teams of scientists have resolved a longstanding controversy surrounding the origins of complex life on Earth.

The joint studies found molecular fossils extracted from 635-million-year-old rocks aren't the earliest evidence of animals, but instead common algae.

The researchers from The Australian National University (ANU), Max Planck Institute and Caltech say the finding has big implications for our understanding of evolution.

"It brings the oldest evidence for animals nearly 100 million years closer to the present day," Dr Lennart van Maldegem from ANU, co-author author of one study, said.

"We were able to demonstrate that certain molecules from common algae can be altered by geological processes - leading to molecules which are indistinguishable from those produced by sponge-like animals.

Professor Jochen Brocks, also based at ANU, said the mystery of when our very earliest animal ancestors emerged and became abundant in the oceans has puzzled palaeontologists for more than a century.

"Ten years ago, scientists discovered the molecular fossils of an animal steroid in rocks that were once at the bottom of an ancient sea in the Middle East," Professor Brocks said.

"The big question was, how could these sponges have been so abundant, covering much of the seafloor across the world, but leave no body fossils?"

Dr Ilya Bobrovskiy, lead author of the other study, said the researchers have been able to "solve this mystery".

"While it holds true sponges are the only living organism which can produce these steroids, chemical processes can mimic biology and transform common and abundant algae sterols into 'animal' sterols," he said.

"These molecules can be generated in the lab when simulating geological time and temperatures, but we also showed such processes did happen in ancient rocks."

Researchers have developed a new theory for observing a quantum vacuum that could lead to new insights into the behaviour of black holes.

The Unruh effect combines quantum physics and the theory of relativity. So far it has not been possible to measure or observe it, but now new research from a team led by the University of Nottingham has shed light on how this could be achieved using sound particles. The team's research has been published today in the journal Physical Review Letters.

The Unruh effect suggests that if you fly through a quantum vacuum with extreme acceleration, the vacuum no longer looks like a vacuum: rather, it looks like a warm bath full of particles. This phenomenon is closely related to the Hawking radiation from black holes.

A research team from the University of Nottingham's Black Hole Laboratory in collaboration with University of British Columbia and Vienna University of Technology has shown that instead of studying the empty space in which particles suddenly become visible when accelerating, you can create a two-dimensional cloud of ultra-cold atoms (Bose-Einstein condensate) in which sound particles, phonons, become audible to an accelerated observer in the silent phonon vacuum. The sound is not created by the detector, rather it is hearing what is there just because of the acceleration (a non-accelerated detector would still hear nothing).

The vacuum is full of particles

One of the basic ideas of Albert Einstein's theory of relativity is: Measurement results can depend on the state of motion of the observer. How fast does a clock tick? How long is an object? What is the wavelength of a ray of light? There is no universal answer to this, the result is relative - it depends on how fast the observer is moving. But what about the question of whether a certain area of space is empty or not? Shouldn't two observers at least agree on that?

No - because what looks like a perfect vacuum to one observer can be a turbulent swarm of particles and radiation to the other. The Unruh effect, discovered in 1976 by William Unruh, says that for a strongly accelerated observer the vacuum has a temperature. This is due to so-called virtual particles, which are also responsible for other important effects, such as Hawking radiation, which causes black holes to evaporate.

"To observe the Unruh effect directly, as William Unruh described it, is completely impossible for us today," explains Dr. Sebastian Erne who came from the University of Nottingham to the Atomic Institute of the Vienna University of Technology as an ESQ Fellow a few months ago. "You would need a measuring device accelerated to almost the speed of light within a microsecond to see even a tiny Unruh-effect -we can't do that." However, there is another way to learn about this strange effect: using so-called quantum simulators.

Quantum simulators

"Many laws of quantum physics are universal. They can be shown to occur in very different systems. One can use the same formulas to explain completely different quantum systems," says Jörg Schmiedmayer from the Vienna University of Technology. "This means that you can often learn something important about a particular quantum system by studying a different quantum system."

"Simulating one system with another has been especially useful for understanding black holes, since real black holes are effectively inaccessible," Dr. Cisco Gooding from the Black Hole laboratory emphasizes. "In contrast, analogue black holes can be readily produced right here in the lab."

This is also true for the Unruh effect: If the original version cannot be demonstrated for practical rea-sons, then another quantum system can be created and examined in order to see the effect there.

Atomic clouds and laser beams

Just as a particle is a "disturbance" in empty space, there are disturbances in the cold Bose-Einstein condensate - small irregularities (sound waves) that spread out in waves. As has now been shown, such irregularities should be detectable with special laser beams. Using special tricks, the Bose-Einstein condensate is minimally disturbed by the measurement, despite the interaction with the laser light.

Jörg Schmiedmayer explains: "If you move the laser beam, so that the point of illumination moves over the Bose-Einstein condensate, that corresponds to the observer moving through the empty space. If you guide the laser beam in accelerated motion over the atomic cloud, then you should be able to detect disturbances that are not seen in the stationary case - just like an accelerated observer in a vacuum would perceive a heat bath that is not there for the stationary observer."

"Until now, the Unruh effect was an abstract idea," says Professor Silke Weinfurtner who leads the Black Hole laboratory at the University of Nottingham, "Many had given up hope of experimental verification. The possibility of incorporating a particle detector in a quantum simulation will give us new insights into theoretical models that are otherwise not experimentally accessible. "?

Preliminary planning is already underway to carry out a version of the experiment using superfluid helium at the University of Nottingham. "It is possible, but very time-consuming and there are technical hurdles for us to overcome," explains Jörg Schmiedmayer. "But it would be a wonderful way to learn about an important effect that was previously thought to be practically unobservable."

The condition trimethylaminuria, is more commonly known as fish odour syndrome, it currently has no cure.

The syndrome occurs when an unpleasant smelling chemical trimethylamine (TMA) can't be broken down by the liver into a different chemical that doesn't smell.

Researchers at the University of Warwick have been able to stabilise and inhibit the enzyme that produces TMA, which means once a drug has been discovered they can test how it to stop TMA production.

Fish odour syndrome (trimethylaminuria) is a debilitating disease, in which the liver cannot break down the smelly chemical trimethylamine which is produced by enzymes from bacteria residing in the gut leaving people with a fish like odour. Researchers from the University of Warwick are paving the way to prevent the syndrome after a breakthrough in studying the enzyme in the gut which produces trimethylamine.

Currently there is no cure for fish odour syndrome, a condition which causes an unpleasant fishy smell that can affect breath, sweat, pee and vaginal fluids.

The cause of fish odour syndrome is when an enzyme pathway in the gut called CntA/B, produces TMA, this happens when the enzyme breaks down a TMA precursor called L-Carnitine which is found in dairy, fish and meat. If an individual lacks a functional liver enzyme called FMO3, they cannot degrade TMA into a non-smelly chemical form, TMAO (trimethylamine oxide). The TMA then builds up in the body and ends up in bodily fluids.

In the paper, 'Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition and inter-subunit electron transfer' published in the Journal of Biological Chemistry, researchers from the School of Life Sciences at the University of Warwick have specifically focused on the CntA protein of the CntA/B enzyme, to stabilise and study it.

CntA/B is a notoriously hard enzyme to study, but once it was stabilised the research group of Prof. Yin Chen were able to gain insight into how CntA perceives its L-Carnitine substrate, with a 3D crystal structure model and by studying the complete electron transfer pathway they could see how the protein is able to turnover TMA.

Now that it is understood how exactly TMA is produced in the gut and that the enzyme can be inhibited, there are grounds for further research into future discovery of drugs targeting the TMA-producing enzyme in the human gut.

The lead researcher, Dr Mussa Quareshy, from the School of Life Sciences at the University of Warwick comments: "We have identified novel, drug-like inhibitors which can inhibit CntA function and thus TMA formation with the potential to attenuate TMA formation in the gut microbiome. This is vital not only for people who have fish odour syndrome, but also because TMA can accelerate atherosclerosis and heart disease, therefore it's urgency to be targeted by drugs is rather significant."

Using modern nanotechnology, it is possible nowadays to produce structures which have a feature sizes of just a few nanometres. This world of the most minute particles - also known as quantum systems - makes possible a wide range of technological applications, in fields which include magnetic field sensing, information processing, secure communication or ultra-precise time keeping. The production of these microscopically small structures has progressed so far that they reach dimensions below the wavelength of light. In this way, it is possible to break down hitherto existent boundaries in optics and utilize the quantum properties of light. In other words, nanophotonics represent a novel approach to quantum technologies.

As individual photons move in the quantum regime, scientists describe the relevant light sources as quantum emitters that can be embedded in nanodiamonds, among others. These special diamonds are characterized by their very small particle size, which can range from just a few to several hundred nanometres. Researchers at the University of Münster have now succeeded for the first time in fully integrating nanodiamonds into nanophotonic circuits and at the same time addressing several of these nanodiamonds optically. In the process, green laser light is directed onto colour centres in the nanodiamonds, and the individual red photons generated there are emitted into a network of nano-scale optical components. As a result, the researchers can now control these quantum systems in a fully integrated state. The results have been published in the journal Nano Letters.

Background and methodology

Previously, it was necessary to set up bulky microscopes in order to control such quantum systems. With fabrication technologies similar to those for producing chips for computer processors, light can be directed in a comparable way using waveguides (nanofibres) on a silicon chip. These optical waveguides, measuring less than a micrometre, were produced with the electron-beam lithography and reactive ion etching equipment at the Münster Nanofabrication Facility (MNF). "Here, the size of a typical experimental set-up was shrunk to a few hundred square micrometres," explains Assistant Professor Carsten Schuck from the Institute of Physics at the University of Münster, who led the study in collaboration with Assistant Professor Doris Reiter from the Institute of Solid State Theory. "This downsizing not only means that we can save space with a view to future applications involving quantum systems in large numbers," he adds, "but it also enables us, for the first time, to control several such quantum systems simultaneously." In preliminary work prior to the current study, the Münster scientists developed suitable interfaces between the nanodiamonds and nanophotonic circuits. These interfaces were used in the new experiments, implementing the coupling of quantum emitters with waveguides in an especially effective way. In their experiments, the physicists utilized the so-called Purcell effect, which causes the nanodiamond to emit the individual photons with a higher probability into the waveguide, instead of in some random direction.

The researchers also succeeded in running two magnetic field sensors, based on the integrated nanodiamonds, in parallel on one chip. Previously, this had only been possible individually or successively. To make this possible, the researchers exposed the integrated nanodiamonds to microwaves, thus inducing changes of the quantum (spin) state of the colour centres. The orientation of the spin influences the brightness of the nanodiamonds, which was subsequently read out using the on-chip optical access. The frequency of the microwave field and therewith the observable brightness variations depend on the magnetic field at the location of the nanodiamond. "The high sensitivity to a local magnetic field makes it possible to construct sensors with which individual bacteria and even individual atoms can be detected," explains Philip Schrinner, lead author of the study.

First of all, the researchers calculated the nanophotonic interface designs using elaborate 3D simulations, thus determining optimal geometries. They then assembled and fabricated these components into a nanophotonic circuit. After the nanodiamonds were integrated and characterized using adapted technology, the team of physicists carried out the quantum mechanical measurements by means of a set-up customized for the purpose.

"Working with diamond-based quantum systems in nanophotonic circuits allows a new kind of accessibility, as we are no longer restricted by microscope set-ups," says Doris Reiter. "Using the method we have presented, it will be possible in the future to simultaneously monitor and read out a large number of these quantum systems on one chip," she adds. The researchers' work creates the conditions for enabling further studies to be carried out in the field of quantum optics - studies in which nanophotonics can be used to change the photo-physical properties of the diamond emitters. In addition to this there are new application possibilities in the field of quantum technologies, which will benefit from the properties of integrated nanodiamonds - in the field of quantum sensing or quantum information processing, for example.

The next steps will include implementing quantum sensors in the field of magnetometry, as used for example in materials analysis for semi-conductor components or brain scans. "To this end", say Carsten Schuck, "we want to integrate a large number of sensors on one chip which can then all be read out simultaneously, and thus not only register the magnetic field at one place, but also visualize magnetic field gradients in space."