Research Unlocks New Information About Reading Through Visual Dictionary in the Brain (Neuroscience)

The uniquely human ability to read is the cornerstone of modern civilization, yet very little is understood about the effortless ability to derive meaning from written words. Scientists at The University of Texas Health Science Center at Houston (UTHealth) have now identified a crucial region in the temporal lobe, know as the mid-fusiform cortex, which appears to act as the brain’s visual dictionary. While reading, the ability of the human brain to distinguish between a real word such as “lemur” and a made-up word like “urmle” appears to lie in the way that region processes information.

Nitin Tandon, MD, and his research team identified a crucial region in the temporal lobe which appears to act as the brain’s visual dictionary. (Photo by James LaCombe)

These findings were published today in Nature Human Behavior.

“How much the mid-fusiform responds to a word and how quickly it can distinguish between a real and made-up word is highly dependent on how frequently the real word is encountered in everyday language,” said Nitin Tandon, MD, senior author, professor and vice chair in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth. “So short, common words like ‘say’ can be identified quickly but long, infrequent words like ‘murmurings’ take longer to be identified as real words.”

For the study, Nitin Tandon and postdoctoral fellow Oscar Woolnough, PhD, the lead author, used recordings from patients who had electrodes temporarily placed in their brains while undergoing treatment for epilepsy. These recordings were then used to create a visual representation of the early neural processing of written words.

They found that this region, which has been overlooked in many previous studies of reading, compares incoming strings of letters encountered while reading with stored patterns of learned words. After words are identified in this area of the brain, this information is spread to other visual-processing regions of the brain.

“Since word frequency is one of the main factors that determines how fast people can read, it is likely that the mid-fusiform acts as the bottleneck to reading speed,” Tandon said. “We showed that if we temporarily disrupt activity in the mid-fusiform cortex using briefly applied electrical pulses, it causes a temporary inability to read, a dyslexia, but doesn’t disrupt other language functions like naming visual objects or understanding speech.”

Tandon said the study serves to improve understanding of how people read and can help people with reading disorders such as dyslexia, the most common learning disability.

Tandon is co-director of the Texas Institute for Restorative Neurotechnologies at UTHealth, faculty in UTHealth Neurosciences and MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, and an attending physician at Memorial Hermann-Texas Medical Center. UTHealth co-authors were Patrick S. Rollo, research associate, and Kiefer J. Forseth, an MD/PhD student at MD Anderson UTHealth Graduate School.

Other co-authors were from the University of Bucharest, Romania; Universite Paris-Sud and Universite Paris-Saclay, France; Johns Hopkins Medical Center, Baltimore; Rice University, Houston; and College de France, Paris.

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health, via the BRAIN Initiative (grant NS098981).

References: http://dx.doi.org/10.1038/s41562-020-00982-w

Provided by University of Texas Health Science Center at Houston

Does your Pain Feel Different in English and Spanish? (Psychology)

A new study out of the University of Miami suggests that the language a bilingual speaks can affect their pain, depending on the cultural associations they tie to each language.

We take for granted the fact that feelings such as love, happiness, or pain are described with different words and expressions across languages. But are these differences in the ways we express these feelings in different languages also tied to differences in the sensations themselves? Would a painful event like a stubbed toe or a bee sting hurt less if a bilingual chose to describe or think about it in Spanish as opposed to English?

©Dreamstime

These sorts of question were central to the development of a recent study by Morgan Gianola, University of Miami psychology graduate student, along with his advisor, Dr. Elizabeth Losin, director of the Social and Cultural Neuroscience lab at the University of Miami, and Dr. Maria Llabre, professor and associate chair of the Department of Psychology at the University of Miami. The study, entitled “Effects of Language Context and Cultural Identity on the Pain Experience of Spanish-English Bilinguals,” is published in the journal Affective Science and will appear as part of the journal’s special issue on “Language and Affect.”

The Social and Cultural Neuroscience lab uses experimental interactions among research participants to assess how social factors, like the language one speaks or the cultural identity they express, can influence pain responses and other clinically relevant behaviors. Gianola joined this lab to research how social environments and cultural learning can be relevant to perceptions as seemingly objective and inherent as pain.

In the study, 80 bilingual Hispanic/Latino participants from the University of Miami and Miami-Dade County communities visited the lab to participate in separate English and Spanish testing sessions; during both sessions, they received a pain-induction procedure, when an experimenter applied painful heat to their inner forearm. The primary difference between the two experimental visits was the language being spoken (English or Spanish), while the painful procedure itself did not change. Participants provided subjective ratings of their pain, and their physiological responses (i.e. their heart rate and palm sweating) were also monitored.

Gianola explained that this study was inspired by previous research in the field of “linguistic relativity,” which has shown differences between English and Spanish speakers in cognitive processes like memory for specific events or categorization of objects. These cognitive differences are also seen among bilinguals when they switch between English and Spanish contexts. Gianola hoped to clarify how such psychological differences across languages might also relate to changes in physical and emotional experiences, like pain.

“All of our participants identified as bicultural,” said Gianola. “After each experimental session, we had them fill out surveys about things like how often they use each language [English and Spanish] and how strongly they relate to and identify with both the Hispanic and U.S.-American sides of their cultural identity. The interesting thing we found was, rather than participants always showing higher pain ratings in Spanish, for example, they tended to report more intense pain and show larger physiological responses to pain when they spoke the language of their stronger cultural identity.”

According to the study findings, participants who engaged more with Hispanic culture showed higher pain when speaking Spanish, while more U.S.-American identified participants reported higher pain in English. People who were fairly balanced in their engagement with U.S.-American and Hispanic culture had pain outcomes that didn’t differ much across languages. The study also suggests that bodily responses to the pain played a larger role in determining pain ratings among more Hispanic oriented bilingual participants.

“This study highlights, first, that Hispanic/Latino communities are not monolithic, and that the factors affecting bilinguals’ psychological and physiological responses to pain can differ across individuals,” said Gianola. “We also see that language can influence such a seemingly basic perception as pain, but that the cultural associations people carry with them may dictate to what extent the language context makes a difference.”

Moving forward, the researchers are developing new experiments to further address the role language plays in influencing cognition and perception among bilinguals. As part of a dissertation project, Gianola plans to investigate the brain processes that contribute to the effects found in this most recent study.

References: Morgan Gianola et al, Effects of Language Context and Cultural Identity on the Pain Experience of Spanish–English Bilinguals, Affective Science (2020). DOI: 10.1007/s42761-020-00021-x

Provided by University of Miami

How SARS-CoV-2 Reaches the Brain? (Neuroscience)

Using post-mortem tissue samples, a team of researchers from Charité – Universitätsmedizin Berlin have studied the mechanisms by which the novel coronavirus can reach the brains of patients with COVID-19, and how the immune system responds to the virus once it does. The results, which show that SARS-CoV-2 enters the brain via nerve cells in the olfactory mucosa, have been published in Nature Neuroscience*. For the first time, researchers have been able to produce electron microscope images of intact coronavirus particles inside the olfactory mucosa.

An electron microscope image (ultrathin section, artificially colored) shows a section of a ciliated cell in the olfactory mucosa. Large numbers of intact SARS-CoV-2 particles (red) are found both inside the cell and on cellular processes. Yellow: kinocilia. © Photo: Michael Laue/RKI & Carsten Dittmayer/Charité

It is now recognized that COVID-19 is not a purely respiratory disease. In addition to affecting the lungs, SARS-CoV-2 can impact the cardiovascular system, the gastrointestinal tract and the central nervous system. More than one in three people with COVID-19 report neurological symptoms such as loss of, or change in, their sense of smell or taste, headaches, fatigue, dizziness, and nausea. In some patients, the disease can even result in stroke or other serious conditions. Until now, researchers had suspected that these manifestations must be caused by the virus entering and infecting specific cells in the brain. But how does SARS-CoV-2 get there? Under the joint leadership of Dr. Helena Radbruch of Charité’s Department of Neuropathology and the Department’s Director, Prof. Dr. Frank Heppner, a multidisciplinary team of researchers has now traced how the virus enters the central nervous system and subsequently invades the brain.

As part of this research, experts from the fields of neuropathology, pathology, forensic medicine, virology and clinical care studied tissue samples from 33 patients (average age 72) who had died at either Charité or the University Medical Center Göttingen after contracting COVID-19. Using the latest technology, the researchers analyzed samples taken from the deceased patients’ olfactory mucosa and from four different brain regions. Both the tissue samples and distinct cells were tested for SARS-CoV-2 genetic material and a ‘spike protein’ which is found on the surface of the virus. The team provided evidence of the virus in different neuroanatomical structures which connect the eyes, mouth and nose with the brain stem. The olfactory mucosa revealed the highest viral load. Using special tissue stains, the researchers were able to produce the first-ever electron microscopy images of intact coronavirus particles within the olfactory mucosa. These were found both inside nerve cells and in the processes extending from nearby supporting (epithelial) cells. All samples used in this type of image-based analysis must be of the highest possible quality. To guarantee this was the case, the researchers ensured that all clinical and pathological processes were closely aligned and supported by a sophisticated infrastructure.

“These data support the notion that SARS-CoV-2 is able to use the olfactory mucosa as a port of entry into the brain,” says Prof. Heppner. This is also supported by the close anatomical proximity of mucosal cells, blood vessels and nerve cells in the area. “Once inside the olfactory mucosa, the virus appears to use neuroanatomical connections, such as the olfactory nerve, in order to reach the brain,” adds the neuropathologist. “It is important to emphasize, however, that the COVID-19 patients involved in this study had what would be defined as severe disease, belonging to that small group of patients in whom the disease proves fatal. It is not necessarily possible, therefore, to transfer the results of our study to cases with mild or moderate disease.”

Immunofluorescence staining shows a nerve cell (pink) inside the olfactory mucosa which has been infected with SARS-CoV-2 (yellow). Supporting (epithelial) cells appear blue. © Photo: Jonas Franz/Universitätsmedizin Göttingen

The manner in which the virus moves on from the nerve cells remains to be fully elucidated. “Our data suggest that the virus moves from nerve cell to nerve cell in order to reach the brain,” explains Dr. Radbruch. She adds: “It is likely, however, that the virus is also transported via the blood vessels, as evidence of the virus was also found in the walls of blood vessels in the brain.” SARS-CoV-2 is far from the only virus capable of reaching the brain via certain routes. “Other examples include the herpes simplex virus and the rabies virus,” explains Dr. Radbruch.

The researchers also studied the manner in which the immune system responds to infection with SARS-CoV-2. In addition to finding evidence of activated immune cells in the brain and in the olfactory mucosa, they detected the immune signatures of these cells in the cerebral fluid. In some of the cases studied, the researchers also found tissue damage caused by stroke as a result of thromboembolism (i.e. the obstruction of a blood vessel by a blood clot). “In our eyes, the presence of SARS-CoV-2 in nerve cells of the olfactory mucosa provides good explanation for the neurologic symptoms found in COVID-19 patients, such as a loss of the sense of smell or taste,” explains Prof. Heppner. “We also found SARS-CoV-2 in areas of the brain which control vital functions, such as breathing. It cannot be ruled out that, in patients with severe COVID-19, presence of the virus in these areas of the brain will have an exacerbating impact on respiratory function, adding to breathing problems due to SARS-CoV-2 infection of the lungs. Similar problems might arise in relation to cardiovascular function.”

References: Meinhardt J et al., Olfactory transmucosal SARS-CoV-2 invasion as port of central nervous system entry in individuals with COVID-19. Nat Neurosci 2020. doi: 10.1038/s41593-020-00758-5 https://www.nature.com/articles/s41593-020-00758-5

Provided by Charité

Laboratory Experiments Unravelling the Mystery of the Mars Moon Phobos (Planetary Science)

What causes the weathering of the Mars moon Phobos? Results from TU Wien give new insights, soon a spacecraft will retrieve soil samples.

Of course, there is no weather in our sense of the word in space – nevertheless, soil can also “weather” in the vacuum of space if it is constantly bombarded by high-energy particles, such as those emitted by the sun. The Martian moon Phobos is affected by a special situation: it is so close to Mars that not only the solar wind but also the irradiation by particles from Mars plays a decisive role there. A research team from TU Wien has now been able to measure this in laboratory experiments. In just a few years, a Japanese space mission will take soil samples from Phobos and bring them back to Earth.

Paul Szabo in the lab at TU Wien. ©TU Wien

Billions of years of particle irradiation

“There are different theories of how the Mars moon Phobos could have formed”, says Paul Szabo, who is working on his PhD thesis in the research group of Prof. Friedrich Aumayr at the Institute of Applied Physics at TU Wien. “It is possible that Phobos was originally an asteroid that was then captured by Mars, but it could also have been created by a collision of Mars with another large object.”

When investigating such celestial bodies, one must always bear in mind that their surfaces have been completely changed over billions of years by cosmic particle bombardment. The surface of the Earth remains unaffected by this, because our atmosphere shields the particles. However, the geology of celestial bodies without atmospheres, such as our Moon or Phobos, can only be understood if it is possible to correctly assess “space weathering”.

Therefore, elaborate experiments were conducted at TU Wien: “We used a mineral like it is found on Phobos and bombarded it in vacuum chambers with different charged particles,” explains Paul Szabo. “Using an extremely precise balance, we can measure how much material is removed in the process and how much each particle affects the surface.

The Mars moons Phobos and Daimos © NASA/JPL-Caltech/University of Arizona
1/3 images

The special properties of the moon Phobos must be taken into account: Its distance from the surface of Mars is less than 6000 km – not even two percent of the distance between our Moon and the Earth. Just like our Moon, it is in a tidally locked rotation around its planet: The same side always faces Mars.

“Because of the extremely small distance between Mars and Phobos, not only particles emitted from the Sun play a role on the surface of Phobos, but also particles from Mars,” says Paul Szabo. The Martian atmosphere consists mainly of carbon dioxide. But in the outer regions of the atmosphere there are also larger amounts of oxygen. When particles from the solar wind penetrate there, oxygen ions can be created, which then hit Phobos at high speed and change the surface material.

Data for 2024 space mission

“With our measuring methods we were able to estimate the erosion of Phobos much more accurately than was previously possible,” says Friedrich Aumayr. “Our results show that the effect of oxygen ions from the Martian atmosphere cannot be neglected. It is also important to distinguish between the two sides of Phobos: While the solar wind causes the weathering on the side facing away from Mars, the bombardment from the Martian atmosphere dominates on the other side, when the Sun is shielded from Mars.

These considerations could soon play an important role in the evaluation of real Phobos samples: As early as 2024, a spacecraft is meant to reach Phobos as part of the Japanese space mission MMX (Martian Moon eXploration) and bring soil samples back to Earth.

References: Szabo, P. S., Biber, H., Jäggi, N., Wappl, M., Stadlmayr, R., Primetzhofer, D., et al. (2020). Experimental insights into space weathering of phobos: laboratory investigation of sputtering by atomic and molecular planetary ions. Journal of Geophysical Research: Planets, 125, e2020JE006583. https://agupubs.onlinelibrary.wiley.com/doi/10.1029/2020JE006583 https://doi.org/10.1029/2020JE006583

Provided by Tu Wein

Airplane Noise at Night can Trigger Cardiovascular Death (Medicine)

For the first time, a study demonstrated that loud night-time noise from airplanes can trigger a cardiovascular death within two hours. Researchers from the University of Basel, the Swiss Tropical and Public Health Institute (Swiss TPH) and partners compared mortality data with acute night-time noise exposure around Zurich airport between 2000 and 2015. The results of the study have been published in the European Heart Journal.

Airplane noise can trigger cardiovascular death, new study finds. (Image: khunaspix/123RF)

Most studies on transportation noise and cardiovascular mortality have focused on long-term exposure to noise. These studies demonstrated that chronic noise exposure is a risk factor for cardiovascular mortality. Across Europe, 48,000 cases of ischemic heart disease per year can be attributed to noise exposure, in particular to road traffic noise.

For the first time, a study led by researchers at Swiss TPH found that acute noise from airplanes during the night can trigger cardiovascular deaths within two hours of aircraft noise exposure. The study published today in the European Heart Journal found that the risk of a cardiovascular death increases by 33% for night-time noise levels between 40 and 50 decibels and 44% for levels above 55 decibels.

“We found that aircraft noise contributed to about 800 out of 25,000 cardiovascular deaths that occurred between 2000 and 2015 in the vicinity of Zurich airport. This represents three percent of all observed cardiovascular deaths,” said Martin Röösli, Professor of Environmental Epidemiology at the University of Basel and Head of the Environmental Exposures and Health unit at Swiss TPH.

According to Röösli, the results are similar to the effects that emotions such as anger or excitement have on cardiovascular mortality. “This is not so surprising, as we know night-time noise causes stress and affects sleep,” he added. The night-time noise effect was more pronounced in quiet areas with little railway and road traffic background noise and for people living in older houses, which often have less insulation and are thus more noise-prone.

The Zurich airport has a flight curfew from 23:30 to 6:00. “Based on our study results, we can deduce that this night-time flight ban prevents additional cardiovascular deaths,” said Röösli.

Innovative study design to exclude confounding factors

The study used a case-crossover design to evaluate whether aircraft noise exposure at the time of a death was unusually high compared to randomly chosen control time periods. “This study design is very useful to study acute effects of noise exposure with high day-to-day variability such as for airplane noise, given changing weather conditions or flight delays,” said PhD student Apolline Saucy, first author of the study. ”With this temporal analysis approach, we can isolate the effect of unusually high or low levels of noise on mortality from other factors. Lifestyle characteristics such as smoking or diet cannot be a bias in this study design.”

Noise exposure was modelled using a list of all aircraft movements at Zurich Airport between 2000 and 2015 and linking with pre-existing outdoor aircraft noise exposure calculations, specific for aircraft type, air route, time of day and year.

References: Apolline Saucy, Beat Schäffer, Louise Tangermann, Danielle Vienneau, Jean-Marc Wunderli, Martin Röösli, “Does nighttime aircraft noise trigger mortality? A case-crossover study on 24,886 cardiovascual deaths“, European Heart Journal (2020), doi: 10.1093/eurheartj/ehaa957 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa957/6007462

Provided by University of Basel

Molecular Mechanism Of Long-term Memory Discovered (Neuroscience)

Researchers at the University of Basel have discovered a molecular mechanism that plays a central role in intact long-term memory. This mechanism is also involved in physiological memory loss in old age.

At the cell and molecule level, many memory functions are nearly identical from life form to life form. (Symbolic image: Birth Into Being / Flickr CC BY-NC-SA 2.0)

Many life forms, from worms to humans, have differentiated memory functions, such as short-term and long-term memory. Interestingly, at the cell and molecule level, many of these functions are nearly identical from life form to life form. Detecting the molecules involved in memory processes is of great importance to both basic and clinical research, since it can point the way to the development of drugs for memory disorders.

By studying roundworms (Caenorhabditis elegans), scientists at the Transfaculty Research Platform for Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now discovered a molecular mechanism of long-term memory that is also involved in memory loss in old age. They report on their findings in the journal Current Biology.

The team led by Dr Attila Stetak, Professor Andreas Papassotiropoulos and Professor Dominique de Quervain used sensory stimuli to first examine the learning and memory ability of genetically modified roundworms lacking a certain gene, mps-2. This gene contains the blueprint for part of a voltage-dependent ion channel in the nerve cell membrane and is suspected of playing a role in memory functions.

It was found that modified worms had equally good short-term memory as unmodified specimens. However, as the length of the experiment increased, the researchers found that the genetically modified worms were less able to retain what they learned. Without mps-2, they had a reduced long-term memory.

Age-related memory loss

In roundworms, as in humans, a loss of memory can be observed with increasing age. However, the molecular basis for this process is largely unclear. In further experiments, the researchers were able to prove that unmodified worms with the mps-2 gene exhibit a strong reduction of the MPS-2 protein, the product of the gene, in old age. This was related to reduced memory performance.

NHR-66 in the roundworm C. elegans, marked with red fluorescent protein. (Photo: University of Basel, MCN)

This lack of MPS-2 protein proved not to be a passive but an actively regulated process. The research team was able to identify another protein, NHR-66, as responsible for regulating this deficiency. NHR-66 actively curbs the reading of the mps-2 gene and thus production of the MPS-2 protein in old age. If in older worms MPS-2 protein level was artificially induced or their NHR-66 was turned off, they had a similarly good memory as younger worms. Both molecules, MPS-2 and NHR-66, therefore make for interesting targets for drugs that could mitigate age-related memory loss. In further studies, the researchers want to examine therapeutic options based on their discovery.

References: Fenyves BG, Arnold A, Gharat VG, Haab C, Tishinov K, Peter F, de Quervain DJF, Papassotiropoulos A, Stetak A., “Dual role of an mps-2/KCNE-dependent pathway in long-term memory and age-dependent cognitive decline”, Current Biology (2020), doi: 10.1016/j.cub.2020.10.069

Provided by University of Basel

A Shapeshifting Material Based on Inorganic Matter (Material Science)

By embedding titanium-based sheets in water, a group led by scientists from the RIKEN Center for Emergent Matter Science has created a material using inorganic materials that can be converted from a hard gel to soft matter using temperature changes. Science fiction often features inorganic life forms, but in reality, organisms and devices that respond to stimuli such as temperature changes are nearly always based on organic materials, and hence, research in the area of “adaptive materials” has almost exclusively focused on organic substances. However, there are advantages to using inorganic materials such as metals, including potentially better mechanical properties. Considering this, the RIKEN-led group decided to attempt to recreate the behavior displayed by organic hydrogels, but using inorganic materials. The inspiration for the material comes from an aquatic creature called a sea cucumber. Sea cucumbers are fascinating animals, related to starfishes (but not to cucumbers!)–that have the ability to morph their skin from a hard layer to a kind of jelly, allowing them to throw out their internal organs–which are eventually regrown–to escape from predators. In the case of the sea cucumbers, chemicals released by their nervous systems trigger the change in the configuration of a protein scaffold, creating the change.

Fig. 1: Thermoresponsive hydrogel consisting of inorganic nanosheets (titanate nanosheet; TiNS) and water. a A schematic illustration of unilamellar titanate (IV) nanosheet (TiNS). Countercations are omitted for clarity. Open square indicates vacant sites. b–g Schematic illustrations of the hydrogel of TiNS (TiNS-Gel) in a repulsion-dominant state (TiNS-GelRepuls; b–d) and an attraction-dominant state (TiNS-GelAttract; e–g). When the electrostatic repulsion between TiNSs in an aqueous dispersion is strong enough, TiNSs spontaneously self-assemble into a long-periodicity lamellar architecture (c) in which their mobility is mutually restricted (d). As a result, their aqueous dispersion can exhibit a gel-like behavior, denoted as TiNS-GelRepuls. When TiNS-GelRepuls is heated above a critical temperature, the electrostatic repulsion becomes weaker than the competing van der Waals attraction, so that TiNSs abruptly stack tightly (g) to form an interconnected 3D network that can hold large quantities of water (f), denoted as TiNS-GelAttract. Because of the large difference in the topology of the internal structure between TiNS-GelRepuls and TiNS-GelAttract, this gel-to-gel transition is accompanied by drastic changes in the optical and mechanical properties. © Koki Sano et al.

To make it, the researchers experimented with arranging nanosheets–thin sheets of titanium oxide in this case–in water, with the nanosheets making up 14 percent and water 86 percent of the material by weight.

According to Koki Sano of RIKEN CEMS, the first author of the paper, “The key to whether a material is a soft hydrogel or a harder gel is based on the balance between attractive and repulsive forces among the nanosheets. If the repulsive forces dominate, it is softer, but if the attractive ones are strong, the sheets become locked into a three-dimensional network, and it can rearrange into a harder gel. By using finely tuned electrostatic repulsion, we tried to make a gel whose properties would change depending on temperature.”

The group was ultimately successful in doing this, finding that the material changed from a softer repulsion-dominated state to a harder attraction-dominated state at a temperature of around 55 centigrade. They also found that they could repeat the process repeatedly without significant deterioration. “What was fascinating,” he continues, “is that this transition process is completed within just two seconds even though it requires a large structural rearrangement. This transition is accompanied by a 23-fold change in the mechanical elasticity of the gel, reminiscent of sea cucumbers.”

To make the material more useful, they next doped it with gold nanoparticles that could convert light into heat, allowing them to shine laser light on the material to heat it up and change the structure.

According to Yasuhiro Ishida of RIKEN CEMS, one of the corresponding authors of the paper, “This is really exciting work as it greatly opens the scope of substance that can be used in next-generation adaptive materials, and may even allow us to create a form of ‘inorganic life’.”

References: Sano, K., Igarashi, N., Ebina, Y. et al. A mechanically adaptive hydrogel with a reconfigurable network consisting entirely of inorganic nanosheets and water. Nat Commun 11, 6026 (2020). https://www.nature.com/articles/s41467-020-19905-4 https://doi.org/10.1038/s41467-020-19905-4

Provided by RIKEN

New DNA Scanning Method Could Lead to Quicker Diagnosis of Cancer and Rare Disease (Medicine)

Scientists at the University of Nottingham have made a major breakthrough in genome sequencing, which will enable them to search for the underlying causes of diseases in human DNA quicker than ever before.

Understanding the sequence of human DNA gives scientists information about diseases, including potentially how to diagnose or treat them. In a new paper published in Nature Biotechnology, scientists from the School of Life Sciences at the University have shown that it is now possible to selectively sequence fragments of DNA more quickly and cost effectively than previously, without searching through DNA strands that are not relevant to the biological question, reaching that answer quicker than before.

Professor Matt Loose ©University of Nottingham

This could have major implications in how genetic diseases are understood are diagnosed.

Professor Matt Loose, of the DeepSeq Sequencing Facility in the School of Life Sciences at the University led this project. He said: “In simple terms, we can now sequence the bits of DNA that we want to and ignore bits we don’t. The advances we present here mean we can search through and sequence regions from genomes even as large as the human genome.”

The new study shows how the team can now rapidly scan human genomes and detect genetic abnormalities on the MinION, a portable DNA sequencer. They illustrate this by locating a change in the DNA responsible for a specific type of cancer in less than 15 hours. A human genome has 3 billion data points, and a typical whole genome analysis might take several days. Thus, the team have shown that this method can now be used to ‘scan’ genomes at high speeds to see if there are obvious problems without having to sequence entire genomes, or perform elaborate lab processes to select the genomic regions of interest.

The team have developed a new selective method, called ReadFish, which allows the DNA sequencer to select just those regions of the human genome (or any genome) of interest for a specific question and so only need to use a single sequencing run.

Prof Loose continues: “This breakthrough will enable us to look at a range of applications, such as rapidly searching fragments of the human genome to find evidence of genetic conditions or changes which may lead to illness such as cancer – which would have major implications for diagnosis.

“We are already seeing people using the method to identify the underlying causes for diseases in a host of different individuals for the first time*.”

Alexander Payne, the study’s lead author, says: “Having truly adaptive sequencing, that can respond as the experiment progresses, brings lots of exciting opportunities for customising and tuning your sequencing for the question at hand. I am really looking forward to seeing how ReadFish is used by the nanopore community.”

Gordon Sanghera, CEO of Oxford Nanopore, makers of the real-time, portable sequencing technology on which this work was performed, said “Alexander Payne, Matt Loose and the team have taken advantage of real time sequencing technology to intelligently zoom in on specific areas of interest in the substantial human genome. The potential impact of this work could be profound in enabling more rapid answers, on devices that are small, low cost and easy to use. This research perfectly illustrates our goal of enabling the analysis of any living thing by anyone, anywhere”

The latest study follows on from the team’s previously published research in 2016, where they initially demonstrated the novel technique for highly selective sequencing. This method used real-time nanopore sequencing and enabled, for the first time, people to analyse only DNA strands that contain pre-determined signatures of interest.

In 2018, this same team led an international consortium to sequence the entire human genome on the Oxford Nanopore Technologies hand held pocket sized MinION portable DNA sequencer. At the time this required more than 40 individual sequencing runs on the portable sequencer; the technology had advanced materially since then.

©University of Nottingham

References: Danny E. Miller, Arvis Sulovari, Tianyun Wang, Hailey Loucks, Kendra Hoekzema, Katherine M. Munson, Alexandra P. Lewis, Edith P. Almanza Fuerte, Catherine R. Paschal, Jenny Thies, James T. Bennett, Ian Glass, Katrina M. Dipple, Karynne Patterson, Emily S. Bonkowski, Zoe Nelson, Audrey Squire, Megan Sikes, Erika Beckman, Robin L. Bennett, Dawn Earl, Winston Lee, Rando Allikmets, Seth J. Perlman, Penny Chow, Anne V. Hing, Margaret P. Adam, Angela Sun, Christina Lam, Irene Chang et al., “Targeted long-read sequencing resolves complex structural variants and identifies missing disease-causing variants”, bioRXiv, 2020. https://www.biorxiv.org/content/10.1101/2020.11.03.365395v1 doi: https://doi.org/10.1101/2020.11.03.365395

Provided by University of Nottingham

Warbler Coloration Shaped by Evolution via Distinct Paths (Biology / Ornithology)

Color-related genes help explain how there are so many species of warblers.

Two genes that are important for the diverse colors and patterns of warbler plumage have evolved through two very different processes, according to a new study led by Penn State researchers. These evolutionary processes could help explain the rapid evolution of these songbirds into so many unique species.

According to a new study, the evolution of two color related genes helps explain the striking diversity in colors and patterns among wood warblers, like the blackburnian warbler pictured here. © Darrell Cochran

“Wood warblers are an incredibly colorful and diverse group of birds, with more than a hundred species in total,” said Marcella Baiz, postdoctoral researcher at Penn State and first author of the paper. “These species arose very quickly in evolutionary time in what biologists call a species radiation. To better understand this radiation, we studied genetic regions related to plumage coloration within a particularly colorful subset of warblers.”

The research team sequenced the genomes of all 34 species within the Setophaga genus of wood warblers and created a phylogenetic tree that clarifies how each species is related to one another. Then, they focused on nine closely related pairs of “sister species.” Each pair is the result of one species diverging into two. Seeing if similar evolutionary processes are at play in each of the pairs allowed the researchers to gain a better understanding of the overall radiation.

A paper describing their results appears today (Nov 30.) in the journal Current Biology.

“In most cases it is difficult to get at the genes underlying the diversification process because it can be hard to link specific genes to specific traits, like colors,” said David Toews, assistant professor of biology at Penn State and leader of the research team. “But many species of warblers readily interbreed, producing hybrid offspring with a mix of the parent species’ traits, so we were previously able to link certain color patterns with their underlying genetic regions. In this study, we focused on two coloration genes, but were able to study them across all the species in this large genus, to give us a window into the rest of the radiation.”

The first gene, the Agouti-signaling protein (ASIP), is involved in producing the pigment melanin, which underlies brown and black plumage in these warblers. Within each pair of sister species where there were differences in the amount or location of the black or brown in their plumage, the team predictably found genetic differences near ASIP.

“We created an evolutionary tree based solely on the ASIP gene region, which more clearly shows how the gene has changed across the genus,” said Baiz. “The patterns in this gene tree mirror patterns in the phylogenetic tree based on what we see across the whole genome. This implies that the differences we see in ASIP resulted from mutations that arose independently in different species. However, the gene tree from the second gene, BCO2, showed a very different pattern that did not match up with the whole genome tree, which suggests different processes are at play.”

The second gene, beta-carotene oxygenate 2 (BCO2), is involved in producing carotenoid pigments, which result in bright yellow, red, and orange plumage. The researchers suggest that a process called introgression– the exchange of genes between species that have evolved separately–may explain why the pattern of genetic changes in BCO2 didn’t align with the overall radiation of the group.

The research team found that one color-related gene has undergone a standard mode of evolution, with mutations arising in separate species. By contrast, portions of the second gene in some cases have been transferred between species through a process known as introgression, where hybrid birds mate with a parent species and, over generations, transfer genetic material. ©Todd Fellenbaum

“Introgression can occur when two separate species hybridize, and the hybrid offspring go on to mate with one of the original species,” said Baiz. “After several generations, genetic material from one species can be incorporated into the other. The signal of this kind of ancient introgression can be maintained in the genomes of living individuals–like how ancestry tests can reveal how many Neanderthal genes you have. In this instance, we unexpectedly found evidence for ancient introgression at BCO2 in two otherwise distantly related warblers in this genus.”

The researchers found evidence of introgression involving the yellow warbler and magnolia warbler and involving the prairie warbler and vitelline warbler, all species with colorful carotenoid coloration in their feathers. However, they note that with the current data it is difficult to tell the directionality of the gene transfer.

“One possibility is that the magnolia warbler version of BCO2 introgressed into the yellow warbler, and this ‘new to them’ version produced a broader deposition of carotenoids in the feathers of the yellow warbler,” said Toews. “It is fun to think that ancient introgression is what made the yellow warbler so yellow!”

©Marcella Baiz et al.

This is one of the first examples of carotenoid gene transfer among vertebrates. Collectively, the results of this study suggest that both introgression and a more standard mode of evolution, where mutations occur and are passed from parent to offspring, have played a role in generating the diversity of colors in this genus and could have helped enable the extreme diversification of warblers.

In the future, the researchers hope to link specific mutations in these genes to changes in plumage coloration and to map out the molecular pathways involved in pigment production. They would also like to expand their study to all 110 species of warblers.

“There’s a possibility that there may be introgression from another genus entirely,” said Toews. “Expanding to other warblers would allow us to explore this possibility, and to more broadly understand the radiation of these fascinating birds.”

In addition to Baiz and Toews, the research team includes Andrew Wood, a research technologist at Penn State, Alan Brelsford at the University of California Riverside, and Irby Lovette at the Cornell Lab of Ornithology. The Cornell Lab of Ornithology, the Penn State Eberly College of Science, and the Penn State Huck Institutes of the Life Sciences.

References: Marcella D. Baiz, Andrew W. Wood, Alan Brelsford, Irby J. Lovette, “Pigmentation Genes Show Evidence of Repeated Divergence and Multiple Bouts of Introgression in Setophaga Warblers”, Current Biology, 2020. https://www.cell.com/current-biology/fulltext/S0960-9822(20)31671-7 DOI:https://doi.org/10.1016/j.cub.2020.10.094

Provided by Penn State