Culture

The life-givers of integrated circuits and quantum devices in silicon are small structures made from patches of foreign atoms called dopants. The dopant structures provide charge carriers that flow through the components of the circuit, giving the components their ability to function. These days the dopant structures are only a few atoms across and so need to be made in precise locations within a circuit and have very well-defined electrical properties. At present manufacturers find it hard to tell in a non-destructive way whether they have made their devices according to these strict requirements. A new imaging paradigm promises to change all that.

The imaging mode called broadband electric force microscopy, developed by Dr Georg Gramse at Keysight technologies & JKU uses a very sharp probe that sends electromagnetic waves into a silicon chip, to image and localize dopant structures underneath the surface. Dr Gramse says that because the microscope can use waves with many frequencies it can provide a wealth of previously inaccessible detail about the electrical environment around the dopant structures. The extra information is crucial to predicting how well the devices will ultimately perform.

The imaging approach was tested on two tiny dopant structures made with a templating process which is unique in achieving atomically sharp interfaces between differently doped regions. Dr Tomas Skeren at IBM produced the world's first electronic diode (a circuit component which passes current in only one direction) fabricated with this templating process, while Dr Alex Kölker at UCL created a multilevel 3-D device with atomic scale precision.

The results, published in the journal Nature Electronics, demonstrate that the technique can take pictures and resolve as few as 200 dopant atoms even if they are hidden below the same number of Si atoms. It can tell the difference between certain flavours of dopant atoms, and can also provide information about the way charge carriers move through the structures and about atomic-sized 'traps' that can stop them from moving.

Professor Neil Curson, who leads the group at UCL, said: "This research could not have come at a better time for the massive world-wide effort to make smaller electronics or quantum computers in silicon. While the success in making components smaller and more complicated has been spectacular, the technology required to actually observe what is being made has not been keeping up. This has become a major problem for quality control in silicon chip manufacture and for information security, when you can't see what's inside the chips you are making or buying. Our new research will help solve many of these issues."

Dr Andreas Fuhrer from IBM Research, added: "After learning to make the first tiny dopant device structures consisting of two different dopant species, boron and phosphorous, it was extremely useful to work with this international team to discover subtle details about our structures that would just not be possible in any other way."

New Rochelle, NY, August 5, 2020--Individuals playing a virtual reality (VR)-based game showed a higher navigational efficiency and less disorientation than those playing a non-VR immersive desktop version, according to a study in the peer-reviewed journal Cyberpsychology, Behavior, and Social Networking. Click here to read the article now.

Navigation in VR can be overwhelming for its users.

"Participants in the VR condition performed better on spatial-based knowledge questions," said Egon van den Broek, PhD, Utrecht University, The Netherlands, and coauthors.

"An interesting use of VR, in addition to education and training, is its use to rehabilitate decreases occurring in navigational abilities and spatial memory in older individuals," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.

The experimental vaccine against SARS-CoV-2 that was the first to enter human trials in the United States has been shown to elicit neutralizing antibodies and a helpful T-cell response with the aid of a carefully engineered spike protein that mimics the infection-spreading part of the virus.

The latest paper about a Moderna-NIH vaccine that recently entered phase 3 human trials was published today in the journal Nature; its leading authors are Barney Graham and Kizzmekia Corbett at the National Institute of Allergy and Infectious Diseases' (NIAID) Vaccine Research Center, part of the National Institutes of Health, and Andrea Carfi of biotech company Moderna. It describes both preclinical results and important protein engineering led by a team at The University of Texas at Austin.

The paper describes in part work to stabilize an otherwise-shifting part of the virus: the protein that fuses with and infects cells, called the spike protein. Earlier research into coronaviruses was critical for the fastest-ever progression from virus genome sequencing to vaccine testing in humans, which took only 66 days.

"Several things were key for rapid vaccine development, including understanding the precise atomic-level structure of the spike protein and how to stabilize it," said UT Austin associate professor of molecular biosciences Jason McLellan, an author on the paper. "As fast as this all happened, the development was possible because of years of earlier research."

The members of the NIAID team and McLellan laboratory at UT Austin announced earlier this year that they had mapped the molecular structure of a stabilized spike protein within weeks of receiving the genetic sequence, publishing the structure of the SARS-CoV-2 spike protein in the journal Science. NIAID and the biotechnology company Moderna, based in Cambridge, Massachusetts, worked to develop a messenger RNA (mRNA) vaccine, which, according to the NIH, directs the body's cells to express the spike in its prefusion conformation to elicit an immune response. Today's paper describes findings that the vaccine keeps infection from spreading into the airways of mice, produces neutralizing antibodies and prompts a response in immune cells called memory T-cells.

The stabilized spike protein, known as the S-2P protein, also features in several other coronavirus vaccines currently in clinical trials.

The SARS-CoV-2 spike protein is a shape-shifter, changing its structure before and after fusing with cells. The immune system responds best when the spike protein is in its prefusion shape, so McLellan's team reengineered the protein in two key places to lock it into that shape.

McLellan's postdoctoral researcher Nianshuang Wang had identified genetic mutations necessary to stabilize the shape-shifting spike protein for MERS-CoV back in 2017, and the team found the same tactic works with the new coronavirus. Using small genetic modifications to the gene sequence that encodes for the protein, the researchers essentially make part of the spring-loaded portion of the molecule more rigid, preventing it from rearranging.

Instead of a painful process of trial and error, the researchers designed the necessary mutations within about a day of receiving the SARS-CoV-2 virus genome. The McLellan lab completed the atomic-level structure, and graduate student Daniel Wrapp harvested and purified the spike protein. Soon after, Corbett and Graham at the NIAID verified that the S-2P protein generated potent antibodies in mice.

Scientists have developed a new prediction of the shape of the bubble surrounding our solar system using a model developed with data from NASA missions.

All the planets of our solar system are encased in a magnetic bubble, carved out in space by the Sun's constantly outflowing material, the solar wind. Outside this bubble is the interstellar medium -- the ionized gas and magnetic field that fills the space between stellar systems in our galaxy. One question scientists have tried to answer for years is on the shape of this bubble, which travels through space as our Sun orbits the center of our galaxy. Traditionally, scientists have thought of the heliosphere as a comet shape, with a rounded leading edge, called the nose, and a long tail trailing behind.

Research published in Nature Astronomy in March and featured on the journal's cover for July provides an alternative shape that lacks this long tail: the deflated croissant.

The shape of the heliosphere is difficult to measure from within. The closest edge of the heliosphere is more than ten billion miles from Earth. Only the two Voyager spacecraft have directly measured this region, leaving us with just two points of ground-truth data on the shape of the heliosphere.

From near Earth, we study our boundary to interstellar space by capturing and observing particles flying toward Earth. This includes charged particles that come from distant parts of the galaxy, called galactic cosmic rays, along with those that were already in our solar system, travel out towards the heliopause, and are bounced back towards Earth through a complex series of electromagnetic processes. These are called energetic neutral atoms, and because they are created by interacting with the interstellar medium, they act as a useful proxy for mapping the edge of the heliosphere. This is how NASA's Interstellar Boundary Explorer, or IBEX, mission studies the heliosphere, making use of these particles as a kind of radar, tracing out our solar system's boundary to interstellar space.

To make sense of this complex data, scientists use computer models to turn this data into a prediction of the heliosphere's characteristics. Merav Opher, lead author of the new research, heads a NASA- and NSF-funded DRIVE Science Center at Boston University focused on the challenge.

This latest iteration of Opher's model uses data from NASA planetary science missions to characterize the behavior of material in space that fills the bubble of the heliosphere and get another perspective on its borders. NASA's Cassini mission carried an instrument, designed to study particles trapped in Saturn's magnetic field, that also made observations of particles bouncing back towards the inner solar system. These measurements are similar to IBEX's, but provide a distinct perspective on the heliosphere's boundary.

Additionally, NASA's New Horizons mission has provided measurements of pick-up ions, particles that are ionized out in space and are picked up and move along with the solar wind. Because of their distinct origins from the solar wind particles streaming out from the Sun, pick-up ions are much hotter than other solar wind particles -- and it's this fact that Opher's work hinges on.

"There are two fluids mixed together. You have one component that is very cold and one component that is much hotter, the pick-up ions," said Opher, a professor of astronomy at Boston University. "If you have some cold fluid and hot fluid, and you put them in space, they won't mix -- they will evolve mostly separately. What we did was separate these two components of the solar wind and model the resulting 3D shape of the heliosphere."

Considering the solar wind's components separately, combined with Opher's earlier work using the solar magnetic field as a dominant force in shaping the heliosphere, created a deflated croissant shape, with two jets curling away from the central bulbous part of the heliosphere, and notably lacking the long tail predicted by many scientists.

"Because the pick-up ions dominate the thermodynamics, everything is very spherical. But because they leave the system very quickly beyond the termination shock, the whole heliosphere deflates," said Opher.

The shape of our shield

The shape of the heliosphere is more than a question of academic curiosity: The heliosphere acts our solar system's shield against the rest of the galaxy.

Energetic events in other star systems, like supernova, can accelerate particles to nearly the speed of light. These particles rocket out in all directions, including into our solar system. But the heliosphere acts as a shield: It absorbs about three-quarters of these tremendously energetic particles, called galactic cosmic rays, that would make their way into our solar system.

Those that do make it through can wreak havoc. We're protected on Earth by our planet's magnetic field and atmosphere, but technology and astronauts in space or on other worlds are exposed. Both electronics and human cells can be damaged by the effects of galactic cosmic rays -- and because galactic cosmic rays carry so much energy, they're difficult to block in a way that's practical for space travel. The heliosphere is spacefarers' main defense against galactic cosmic rays, so understanding its shape and how that influences the rate of galactic cosmic rays pelting our solar system is a key consideration for planning robotic and human space exploration.

The heliosphere's shape is also part of the puzzle for seeking out life on other worlds. The damaging radiation from galactic cosmic rays can render a world uninhabitable, a fate avoided in our solar system because of our strong celestial shield. As we learn more about how our heliosphere protects our solar system -- and how that protection may have changed throughout the solar system's history -- we can look for other star systems that might have similar protection. And part of that is the shape: Are our heliospheric lookalikes long-tailed comet shapes, deflated croissants, or something else entirely?

Whatever the heliosphere's true shape, an upcoming NASA mission will be a boon for unraveling these questions: the Interstellar Mapping and Acceleration Probe, or IMAP.

IMAP, slated for launch in 2024, will map the particles streaming back to Earth from the boundaries of the heliosphere. IMAP will build on the techniques and discoveries of the IBEX mission to shed new light on the nature of the heliosphere, interstellar space, and how galactic cosmic rays make their way into our solar system.

Opher's DRIVE Science Center aims to create a testable model of the heliosphere in time for IMAP's launch. Their predictions of the shape and other characteristics of the heliosphere -- and how that would be reflected in the particles streaming back from the boundary -- would provide a baseline for scientists to compare with IMAP's data.

The COVID-19 pandemic has had detrimental effects on global infrastructure sectors, including economic, political, health care, education and research systems, and there is still no definitive treatment strategy for the disease. A team of scientists, including VCU Massey Cancer Center researcher Masoud Manjili, D.V.M., Ph.D., conducted a comprehensive analysis of worldwide COVID-19 data to identify key strategies moving forward to develop effective therapeutics.

In a critical literature review, among the 20 most-read articles published in the Journal of Immunology in May 2020, Manjili suggests that COVID-19 should be treated as an acute inflammatory disease and that severity of infection is associated with the dysregulation of inflammatory immune responses and subsequent inability to develop protective immunity from the virus.

"Drugs that target the virus or suppress inflammatory immune responses have produced inconsistent results and might not be the best treatment for patients with COVID-19," said Manjili, a member of the Cancer Cell Signaling research program at Massey and a professor in the Department of Microbiology and Immunology at the VCU School of Medicine. "Instead, the use of drugs that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy."

The majority of people infected with COVID-19 show flu-like symptoms and survive the disease. However, individuals with susceptibility factors, including age (65 years and above), sex and underlying health complications such as cancer, heart disease, diabetes or asthma, are significantly more vulnerable to infection because their immune response is in disarray. Manjili said that men are more susceptible to infection than women because of an expression of sex-associated genes coded by the X chromosome that play a key role in the immune response.

"Although over 90 percent of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from COVID-19, those individuals presenting with critical symptoms are in urgent need of treatment options," Manjili said.

Because viral loads are similar in symptomatic and asymptomatic patients with COVID-19, it appears that a dysregulated immune response is the primary cause of death as opposed to viral load, according to Manjili's review. The most serious consequences of COVID-19 are sepsis-like cytokine storm (a severe overreaction of the immune system), blood clots and respiratory or cardiovascular complications.

In response to injury or infection, the immune system will normally react with an immediate inflammatory response to limit the infection and help to develop a long-lasting, protective immunity against the virus within 7-10 days following infection.

"However, when inflammation is not modulated or resolved after serving its purpose, it turns into hyperinflammation or becomes chronic and results in the inhibition of adaptive immune responses, tissue damage or organ failure, as evidenced in many cases of the novel coronavirus," Manjili said. "Therefore, understanding and successfully controlling inflammation would be a promising approach for the management of COVID-19."

Manjili suggests that antiviral therapies such as chloroquine, hydroxychloroquine and remdesevir might be effective as preventive strategies or in very early stages of infection but could prevent patients from gaining protective immunity. Efforts to develop novel treatment options for COVID-19 should be primarily focused on the transference of plasma from immune individuals to those with severe symptoms of the disease as well as a vaccine that prevents infection.

Specifically, Manjili determined that the highly tailored anti-inflammatory drugs, like the blood pressure medication losartan, should be considered as viable options for treating COVID-19.

"The combination of losartan with convalescent plasma in symptomatic patients could be a promising strategy for the prevention or treatment of severe clinical symptoms and will allow patients to develop immunity against the virus," Manjili said.

5 August 2020, Cambridge - A global team of researchers has partnered up with the Māori tribe Ngātiwai to sequence the genome of the tuatara, a rare reptile endemic to New Zealand. Their work, published in the scientific journal Nature, lays the foundation for understanding the evolution of this ancient species, and can inform conservation efforts to protect it. The study included collaborators at the University of Otago and at EMBL's European Bioinformatics Institute (EMBL-EBI).

With its small, scaly body, pointy tail, and clawed feet, the tuatara seems to tick all the boxes to be a lizard - yet it isn't. This ancient reptile is the sole survivor of its own evolutionary branch on the tree of life, the Sphenodontia. Until now, biologists had not reached consensus on the evolutionary history of tuatara - whether they are more closely related to birds, crocodiles, and turtles, or if they stemmed from an ancestor shared with lizards and snakes.

"Our research confirms that tuatara have diverged from the ancestor of lizards and snakes about 250 million years ago," says Matthieu Muffato, the analysis lead from Ensembl comparative genomics at EMBL-EBI. "This long period of independent evolution explains why we found the tuatara genome to be so unlike those of other vertebrates."

A biological curiosity

"The tuatara genome is considerably bigger than the human genome, and it has a unique constitution. It contains a lot of repetitive DNA segments that are unique to the species and have no known function," explains Fergal Martin, Vertebrate Annotation Coordinator at EMBL-EBI.

The sequence of the tuatara genome revealed a number of aspects of this reptile's lifestyle. Although tuatara are predominantly nocturnal animals, their DNA carries a high number of genes involved in colour vision, which might help day-active juveniles escape from their predators.

If they survive the vagaries of their juvenile life, tuatara can live to be more than 100 years old. Scientists examining some of the genes implicated in protecting the body from ageing have found that tuatara have more of these genes than any other vertebrate species yet examined.

"Could this be one of the keys to their long lifespan? Tuatara also don't appear to get many diseases, so looking into what genetic factors might protect them from infection was another point of focus for our study," says Neil Gemmell, Professor and Team Leader at the University of Otago.

A vulnerable icon

"The tuatara is an iconic species, both for the Māori and for biologists. It has a unique biology and its basic body shape hasn't changed much over evolutionary time, so it's a precious species for us to understand what the common ancestor of lizards, snakes, and tuatara was like," explains Paul Flicek, Associate Director of EMBL-EBI Services.

The scientists hope that their findings on the genome and biology of the tuatara will inform conservation efforts to protect this unusual reptile. Tuatara used to thrive in New Zealand before the first human settlers brought invasive predators such as rats 800 years ago. The tuatara's extremely slow life cycle is no match for the voracity of its predators: when it comes to reproduction, tuatara take the scenic route. They sometimes need more than 10 years to reach sexual maturity, and they produce young only every two to five years.

Although the species' conservation status is of "least concern" according to the IUCN Red List of Threatened Species, the tuatara relies on active conservation management to prevent the establishment of invasive species on the islands where it survives.

"Very early on it became clear that a primary goal for us all was to develop new knowledge that would improve the conservation of this species. We agreed to partner together with Ngātiwai to achieve that aim, whilst also looking for opportunities to share other benefits that might derive from the research. It was an informed partnership that I believe was an important enabling element for the project's success, which extends well beyond the scientific achievement of sequencing the genome," says Gemmell.

A McGill research team has developed a new technique to detect nano-sized imperfections in materials. They believe this discovery will lead to improvements in the optical detectors used in a wide range of technologies, from cell phones to cameras and fiber optics, as well as in solar cells.

The researchers, led by Professor Peter Grutter from McGill's Physics Department, used atomic force microscopy to detect the ultrafast forces that arise when light interacts with matter. In their paper, published this week in PNAS, they demonstrate that forces arising from two, time-delayed light pulses can be detected with sub-femtosecond precision (these are millionths of a billionth of a second) and nanometer spatial resolution in a wide range of materials.

Improved technique for using light to detect imperfections in materials

"To understand and improve materials, scientists typically use light pulses faster than 100 femtoseconds to explore how quickly reactions occur and determine the slowest steps in the process," explains Zeno Schumacher, the paper's first author who was a post-doctoral fellow in Grutter's lab when the research was done and is now based at ETH Zurich. "The electric field of a light pulse oscillates every few femtoseconds and will push and pull on the atomic-sized charges and ions that comprise matter. These charged bodies then move, or polarize, under these forces and it is this motion that determines a material's optical properties."

Real materials used in solar cells (also known as photovoltaics) and in the optical detectors used in equipment like cell phones and cameras have many imperfections and defects of different types that are very difficult to characterize, as they are typically only a nanometer in size. Moreover, it has been very challenging to identify and study the 'hot spots' and 'weak links' in the materials that can slow down or hinder light induced processes because traditional techniques for detecting imperfections average over differences in properties at a larger area.

Seeing nanoscale imperfections in a range of materials

The new technique developed by the McGill team combines ultrafast nonlinear optical methods with the high spatial resolution of atomic force microscopy. They have demonstrated that their technique works on an insulating non-linear optical material (LiNbO3) as well as a nanometer thin, two-dimensional semiconducting flake of molybdenum diselenide (MoSe2), an inorganic compound used in optical and scanning-probe microscopy.

"Our new technique is applicable to any material, such as metals, semiconductors and insulators," says Peter Grutter, the senior author on the paper. "It will enable use high spatial and temporal resolution to study, understand and ultimately control for imperfections in photovoltaic materials. Ultimately, it should help us improve solar cells and the optical detectors used in a wide range of technologies."

WASHINGTON - The Center for Justice Research at Texas Southern University and the Black Public Defender Association today released "Save Black Lives: A Call for Racially-responsive Strategies and Resources for the Black Community during the COVID-19 Pandemic," a comprehensive report that details why public health responses and strategies to address COVID-19 must be centered around race and the criminal legal system.

"When the system fails to acknowledge the role that race is playing in the COVID-19 pandemic and develop racially equitable responses, greater harm is inflicted on the Black community, which is being devastated by this disease," said April Frazier Camara, Co-Founder and Chair of Black Public Defender Association.

Black people are being infected and dying from COVID-19 at alarming rates and they are also overrepresented in carceral systems that increase their risk of exposure to this deadly virus. The report shows that race-neutral responses to the pandemic within the criminal legal system are ineffective, and how they cause harm to Black communities.

"This report unpacks the nested structural reality of racial injustice, disciplinary bias, and the lack of attention directed at the practical needs of the historically disenfranchised," said Howard Henderson, Founding Director of the Center for Justice Research.

Solutions to COVID-19 within the criminal legal system should be developed with the expertise of Black public defenders and justice-oriented researchers, who are closest to the problem of mass incarceration and this pandemic.

Key findings and recommendations in the report:

Race-neutral advocacy in criminal legal and public health systems is harmful to Black lives. The first reporting of COVID-19 was presented under the guise of underlying health conditions and age, which soon had race-specific realities. Similarly, much of the advocacy around protecting people in prison has been race-neutral, even though Black people are over represented in carceral systems, and once released, will likely return to communities that are COVID-19 hotspots.

Black public defenders and Black researchers play a critical role in advancing equitable policy solutions to the COVID-19 pandemic within the criminal legal system. As members of a community impacted most severely by COVID-19 and incarceration, their voices are critical to developing culturally-responsive solutions, instead of blanket policies and research findings that fail to account for race or engage the Black community.

The COVID-19 crisis presents an opportunity to fight for decarceration measures that address and reduce racial disparities in the criminal legal system.

Decarceration must be coupled with effective reentry support and services. The overrepresentation of Black people in prisons and jails, combined with the alarmingly high rates of infections and deaths in the general Black population, shows the importance of proper reentry support to prevent the additional spread of this deadly disease. Policymakers have a responsibility to ensure reentry programs are adequately funded because the safety and health of people returning home from prisons and jails, and their communities, depend on it.

The COVID-19 crisis has highlighted that mass incarceration is a public health concern, and even more so, that we need to shift the traditional punishment paradigm of the criminal legal system to the more established approaches of public health and interdisciplinary perspectives for reducing social problems that often cause people to commit crimes.

A 17-year research project has generated a detailed atlas of the genome that reveals the location of hundreds of thousands of potential regulatory regions - a resource that will help all human biology research moving forward.

Of the three billion base pairs in the human genome, only 2% code for the proteins that build and maintain our bodies. The other 98% harbors, among other things, potential regulatory regions - sequences that give cells the instructions and tools needed to turn protein recipes into an astonishingly complex organism. Yet despite their importance and prevalence, non-coding regions have been studied much less than gene-coding sequences, in part because it is more difficult to do so.

The Encyclopedia of DNA Elements (ENCODE) collaboration was launched by the National Human Genome Research Institute with the goal of developing the tools and expertise needed to shed light on our genome's mysterious majority. Now in its final year, ENCODE has made huge advances thanks to the combined scientific and technological prowess of several hundred researchers at dozens of institutions.

"We've sequenced the human genome and we largely know where genes are. But when you get outside genes, mapping the function of genomic 'dark matter' is much more daunting. It's a big step forward for us to know how to find the areas within the 98% that are functionally important," said Len Pennacchio, a senior scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and co-author on 4 of the 15 new ENCODE papers published this week as part of a special collection in Nature. In addition to their original research, Pennacchio and his Berkeley Lab colleagues also provided technical expertise and materials to other ENCODE consortium teams.

Pennacchio said that the project's recent advances will be particularly useful for scientists studying diseases. When trying to determine the underlying causes of a condition, researchers search for genetic variants carried by affected individuals. Sometimes, he said, they find associations with sequences within genes, but often the analyses will pinpoint an area that's far away from any protein-coding sequence, and it isn't readily apparent what that DNA does. Is it important in the heart, or the stomach? Is it important all the time or just at certain phases of development?

"Our datasets give scientists clues as to when and where that sequence functions, and which gene or genes it affects. It gives you an immediate path to follow to learn more, where previously we'd have few hints," he said.

From theory to reality

In the past phases of ENCODE, researchers were focused on identifying all DNA sequences that regulate gene expression, such as promoters and enhancers, and establishing how different regions of our chromosomes are modified and stored (i.e., wrapped around proteins called histones or bound with small tagging molecules). This information reveals a great deal about how cells can express or silence genes differently depending on timing and where they are located in the body. The earlier work was mostly performed on DNA extracted from human cell lines.

"Thanks to ENCODE 2, we had a pretty good map of how DNA is modified along the genome, but what was missing really was the legend for that map," explained Axel Visel, also a Berkeley Lab senior scientist. Visel and Diane Dickel, a research scientist, are co-authors with Pennacchio on the new papers, and all three run the Mammalian Functional Genomics Laboratory within Berkeley Lab's Biosciences Area. "ENCODE phase 3 has been all about understanding what these different modifying marks we found in cell lines really mean in terms of a real organism," Visel added.

For the phase 3 experiments, the Berkeley Lab group, along with numerous other ENCODE consortium teams began applying their analyses to mouse tissues, as the mouse genome is very similar to ours and many of the DNA modifications and on-off switches for gene expression are known to be the same.

The Berkeley Lab team, which has been involved in the project for 12 years, played an especially significant role in ENCODE 3. They are renowned leaders in the use of ChIP-seq, a technique that allows scientists to locate transcription factors and modified proteins on chromatin (the densely packed state that DNA exists in when not activated for transcription or replication), and then to analyze how these molecules are interacting with the sequences. They are also known for their expertise in transgenic assays, a technique used to test if potential gene switches actually function as predicted.

Working closely with Bing Ren at the Ludwig Institute for Cancer Research, the team used ChIP-seq to study the changing landscape of chromatin in embryonic mice and then carried out hundreds of transgenic assays to validate these findings. After thousands of experiments, they generated a dataset covering diverse body tissues at eight developmental stages, significantly expanding the scientific community's knowledge of DNA dynamics during mouse development and creating a resource for biomedical researchers seeking to learn more about human development.

Their atlas, along with nearly 6,000 other datasets on mouse and human DNA regulating elements generated by collaborating research teams, is freely accessible on ENCODE's new online portal.

"Over the years, we've worked extensively with the other groups that were involved in ENCODE and built great complementary relationships," said Dickel. "This is the kind of progress that comes from good collaborations, rather than competition."

For the last leg of the project (ENCODE 4), which is in its final year, participating scientists are using genetically engineered mice to verify and expand upon the discoveries made from studying isolated tissues.

Diabetes seldom occurs in newborns--a condition known as neonatal diabetes. But when it does, it's mostly due to a mutation in a single gene such as the KCNJ11 or insulin (INS). This early-onset type of diabetes differs from type-1 diabetes in that it occurs within the first six months of life and can be either transient or permanent. Most of the mutations that underly this disease prevent the pancreas from producing sufficient insulin, which leads to high blood glucose levels or hyperglycemia.

To understand what causes permanent neonatal diabetes and to find a cure, scientists often use mouse and pig models having Insulin2 (Ins2)C96Y gene mutations. These models develop permanent early-onset diabetes resembling neonatal diabetes. However, a major limitation of these models is that by using them, inter-species transplantation of pancreatic insulin-producing cells (pancreatic beta cells), called islet transplantation, cannot be evaluated, due to adverse immune system reactions characterizing such interspecies transplantation.

Now, in a paper published in Scientific Reports, scientists from Tokyo Tech describe how they established a new mouse model of permanent neonatal diabetes, which exhibits severe insulin-deficiency and beta-cell dysfunction in an immune deficient background. As Professor Shoen Kume, who led the study explains, "We wanted to create a mouse model that would allow us to evaluate the efficacy of transplanting human stem cell-derived or xenogeneic pancreatic beta cells into these mice without having to consider immune responses"

To achieve this goal, the scientists used the CRISPR/Cas9 gene editing technique to introduce a three base pair deletion in the Ins2 gene of a severely-immunodeficient BRJ mouse, that lacked mature T and B lymphocytes and natural killer (NK) cells. This mutation causes a Gln (Q) deletion (p.Q104del), hampering insulin production. The scientists named the mutation 'Kuma mutation'.

Upon examining the Kuma mice as they aged, the scientists discovered that both male and female Kuma mutants developed hyperglycemia three weeks after their birth. They conjectured that this may be due to the low stability of the mutant insulin protein. The scientists also noted that these mice had markedly reduced beta-cell area, size, and mass, as well as a significantly decreased number and size of insulin granules within the beta cells. This meant that the mice could serve as a permanent neonatal diabetes model for islet transplantation.

To corroborate this, their treatment with insulin implants over four weeks successfully reversed their hyperglycemia.

Based on these findings, Prof Kume and his team believe that "the Kuma mutant can not only be used for molecular studies of the Insulin gene and beta cell dysfunction, but its immune-deficient background allows it to be an attractive model for studies examining the functionality of transplanted beta-cells generated from human- or xenogeneic-derived stem cells".

Moreover, as the Kuma mutation is well conserved across different species, the same gene-editing approach can be applied to creating permanent neonatal diabetic models in other animal species, making advancement in the research on this disease condition a little bit easier.

A new way to treat acid mine drainage (AMD) could help transform the environmental pollution problem into an important domestic source of the critical rare earth elements needed to produce technology ranging from smart phones to fighter jets, according to Penn State scientists.

"Acid mine drainage has been a significant environmental concern for many decades," said Mohammad Rezaee, assistant professor of mining engineering in the College of Earth and Mineral Sciences at Penn State. "This research shows we can modify existing treatment processes in a way that not only addresses environmental concerns, but at the same time recovers valuable elements and actually decreases the cost of treatment."

A team of Penn State scientists developed a two-stage treatment process that enabled them to recover higher concentrations of rare earth elements using smaller amounts of chemicals than previously possible, the scientists said.

"This technique represents an efficient, low-cost and environmentally friendly method to extract these valuable minerals that are used in a wide variety of consumer and industrial products," said Sarma Pisupati, professor of energy and mineral engineering and director of the Center for Critical Minerals at Penn State.

Rare earth elements are a group of 17 minerals widely used in advanced technologies and designated by the U.S. as critical to the country's economic and national security. The U.S. currently imports nearly 100% of these materials, with China producing about 85% of the world supply.

AMD from coal mining operations in Appalachia represents a promising domestic source of rare earth elements because it often contains high concentrations of the minerals, and because it is already being collected and treated due to environmental concerns, the scientists said.

"We are currently incurring costs just to treat the water, and in many cases, we are not even collecting all these minerals," Pisupati said. "Now we are able to turn what had been considered a waste product into a valuable resource."

AMD occurs when pyrite rock -- iron sulfide -- unearthed by mining activity interacts with water and air and then oxidizes, creating sulfuric acid. The acid then breaks down surrounding rocks, causing toxic metals to dissolve into the water, the scientists said.

Traditional treatment methods involve collecting the AMD in retention ponds and adding chemicals to neutralize the pH -- an indicator of how acidic or basic a substance is. This causes the dissolved metals to precipitate, or form into solids, and settle out of the water. Up to 70% of rare earth elements can be extracted as a sludge using this process, and the rest are released along with the treated water, according to researchers.

The scientists found they could extract a higher concentration of rare earth elements and other critical minerals by adding carbon dioxide to the AMD and then bringing it to a neutral pH of 7, the target for environmental remediation, in two separate steps.

Using this method, 90% of aluminum was recovered at a pH of 5 and 85% of rare earth elements were recovered by pH 7, the scientists reported in Chemical Engineering Journal.

Adding carbon dioxide to AMD produces chemical reactions that result in the formation of solid minerals called carbonites, the scientists said. The rare earth elements bond with the extra carbonites and precipitate out of the water at lower pH values.

The process, called carbon dioxide mineralization, is an emerging technology being used to remove excess carbon dioxide from the atmosphere. This study represents the first time it has been used to recover large concentrations of rare earth elements from AMD, the scientists said.

Recovering the same concentration of rare earth elements from AMD using traditional treatment methods would require adding additional chemicals to increase the pH beyond 7. The scientists said by lowering recovery costs, the new treatment method could make the domestic rare-earth-element market more competitive.

"With a simple modification of existing treatment processes, industry could use less chemicals and get more value out of AMD waste," Rezaee said. "This is the beauty of this research."

The COVID-19 pandemic exposes weaknesses in the supply chain when countries go into lockdown. Some are small, such as the toilet paper shortages early on, that, while annoying, were eventually resolved. But what happens when the effects of the pandemic reach the food systems of countries highly reliant on food imports and income from abroad, and commerce slows to a halt?

UC Santa Barbara marine conservationist Jacob Eurich and collaborators watched this very situation unfold in the Pacific Island Countries and Territories (PICTs) -- the island nations scattered in the middle of the Pacific Ocean, from New Zealand to French Polynesia, and including the Marshall Islands to Papua New Guinea. While infection with SARS-CoV-2 has been slow there relative to other parts of the world, the global lockdown can have outsized effects on their food systems.

"One of the key messages from the research is to rely less on global food supply chains," said Eurich, a co-author on a paper that appears in the journal Food Security. While this study was specific to the PICT region, areas with few domestic alternatives to global supply chains, he noted, are vulnerable to similar threats to food security when shocks to the system occur.

With their remote locations, lack of arable land and economies dependent on tourism and need for food imports, the PICTs have become reliant on movement in and out of the region for much of the food they consume and also for the money to purchase that food.

But even with commerce slowing down, these countries and territories need not suffer food scarcity and malnutrition, the researchers said. The PICTs are home to large networks of coral reefs that host a diverse array of fish and other seafood.

"Coral reefs should operate as biodiverse, living refrigerators for coastal communities, sourcing replenishable, nutritious food," Eurich said. "Coastal communities can and should be able to depend on traditionally-sourced diets if the resource is healthy."

In fact, the time is ripe to reconsider the role of local production in the region's food systems, according to the researchers. For instance, some areas with farmland could benefit by reinvigorating their production of root crops, which would not only decrease reliance on the global supply chain, but also provide healthy alternatives to imported processed foods.

"Bolstering local production and intraregional trade strengthens the food system," he said. "Consuming more locally produced fresh foods and less non-perishable shelf-stable foods is a step in the right direction."

Meanwhile, a shortening of the supply chain via strong intraregional trade could strengthen the regional economy while also protecting against food insecurity. Significant local processing and storage challenges must be overcome, according to the paper, and intra-island transport and food distribution strengthened. Particularly in the PICT region, where large scale local fish storage is currently inadequate, it helps to prioritize production of less perishable foods (like root crops) over fish, Eurich said.

It's not just about pandemic planning. The same principles for resilient food systems in the face of climate change and natural disaster -- both of which the PICTs have been facing -- could serve as a basis for response to other COVID-19-type scenarios, according to the researchers.

"Climate change and natural disasters can be considered shocks to the system," Eurich said. "The pandemic, while there was time to prepare, was still a shock. We have learned that enhancing storage, production and distribution through coordination and increasing regional transparency are keys of a resilient supply chain when these unexpected changes occur."

Using stem cells to restore lost functions due to spinal cord injury (SCI) has long been an ambition of scientists and doctors. Nearly 18,000 people in the United States suffer SCIs each year, with another 294,000 persons living with an SCI, usually involving some degree of permanent paralysis or diminished physical function, such as bladder control or difficulty breathing.

In a new study, published August 5, 2020 in Cell Stem Cell, researchers at University of California San Diego School of Medicine report successfully implanting highly specialized grafts of neural stem cells directly into spinal cord injuries in mice, then documenting how the grafts grew and filled the injury sites, integrating with and mimicking the animals' existing neuronal network.

Until this study, said the study's first author Steven Ceto, a postdoctoral fellow in the lab of Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, neural stem cell grafts being developed in the lab were sort of a black box.

Although previous research, including published work by Tuszynski and colleagues, had shown improved functioning in SCI animal models after neural stem cell grafts, scientists did not know exactly what was happening.

"We knew that damaged host axons grew extensively into (injury sites), and that graft neurons in turn extended large numbers of axons into the spinal cord, but we had no idea what kind of activity was actually occurring inside the graft itself," said Ceto. "We didn't know if host and graft axons were actually making functional connections, or if they just looked like they could be."

Ceto, Tuszynski and colleagues took advantage of recent technological advances that allow researchers to both stimulate and record the activity of genetically and anatomically defined neuron populations with light rather than electricity. This ensured they knew exactly which host and graft neurons were in play, without having to worry about electric currents spreading through tissue and giving potentially misleading results.

They discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in distinct clusters of neurons with highly correlated activity, much like in the neural networks of the normal spinal cord. When researchers stimulated regenerating axons coming from the animals' brain, they found that some of the same spontaneously active clusters of graft neurons responded robustly, indicating that these networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli, such as a light touch and pinch, also activated graft neurons.

"We showed that we could turn on spinal cord neurons below the injury site by stimulating graft axons extending into these areas," said Ceto. "Putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble into spinal cord-like neural networks that functionally integrate with the host nervous system. After years of speculation and inference, we showed directly that each of the building blocks of a neuronal relay across spinal cord injury are in fact functional."

Tuszynski said his team is now working on several avenues to enhance the functional connectivity of stem cell grafts, such as organizing the topology of grafts to mimic that of the normal spinal cord with scaffolds and using electrical stimulation to strengthen the synapses between host and graft neurons.

"While the perfect combination of stem cells, stimulation, rehabilitation and other interventions may be years off, patients are living with spinal cord injury right now," Tuszynski said. "Therefore, we are currently working with regulatory authorities to move our stem cell graft approach into clinical trials as soon as possible. If everything goes well, we could have a therapy within the decade."

Climate change and disruption of the ecosystem have the potential to profoundly impact the human body. Xue Ming, professor of neurology at Rutgers New Jersey Medical School, who recently published a paper in the International Journal of Environmental Research and Public Health on the effects of climate change on allergies, autoimmunity and the microbiome -- the beneficial microorganisms that live on and inside the human body -- discusses how the delicate balance of the environment affects conditions such as allergies, autism and immune disorders.

How has climate change affected respiratory allergies?

Climate change has worsened respiratory allergic disease and has altered the immune system's tolerance in responding to toxins, which has led to an increase in the prevalence of immune diseases. People with chronic respiratory allergic disease that affects the nose and eyes, such as asthma and allergies, are at particular risk due to increased exposure to pollen and the increased concentration and distribution of air pollutants.

According to the American Academy of Allergy Asthma & Immunology, climate change has both increased the intensity of the pollen season as well as prolonged its duration. Increases in carbon dioxide were shown to lead to an increase in plant reproduction and total pollen levels, especially those plants that thrive at high carbon dioxide concentrations. For example, ragweed pollen has been increasing in concentration, with models predicting that levels will increase by four times within the next 30 years.

Thunderstorms, which have become more frequent due to rising sea temperatures, have been found to increase concentrations of pollen grains at ground level. After absorbing water, these grains can rupture and release allergenic particles that can induce severe asthmatic symptoms in patients with asthma or hay fever.

Climate change has also been linked to increased concentrations and distribution of air pollutants such as ozone, nitric oxide and other volatile organic chemicals. There is a growing body of evidence suggesting that these airborne environmental pollutants may be partially responsible for the substantial increase in allergic respiratory disease seen in industrialized countries over the past several decades.

How do changes to the ecosystem affect allergies and respiratory disorders?

Deforestation and over-logging have led to a dramatic decrease in the diversity of plant species. As one species of plant becomes extinct, new species emerge to take their place. For example, as oak trees have been excessively harvested for architectural purposes, new species of trees have emerged. With these new trees come new forms of tree pollen, which are inhaled and ingested by humans on a daily basis.

Similarly, widespread pesticide use has altered the profile of insects, invertebrates and microorganisms with which we come into contact with through our soil and vegetation. As the environment is altered, our bodies are bombarded with novel organisms. The molecules which make up these organisms -- known as antigens -- are recognized as "foreign" by our bodies and create an inflammatory response.

How might a loss of biodiversity due to climate change affect non-respiratory diseases?

According to the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, biodiversity is declining faster than at any time in human history, with nearly 1 million animal and plant species are threatened with extinction due to climate change.

The loss of biodiversity related to climate change may affect the microbiome, potentially leading to inflammatory, autoimmune and neurologic diseases. Immunologic disorders, such as food allergies, are on the rise. For example, several studies have found that increases in carbon dioxide and temperature are correlated with changes in the composition of the peanut, making it more difficult for the body to adapt immunity.

Could disturbances in gut bacteria affect the autism rate?

Disruption of gut bacteria has been linked to neurologic diseases such as multiple sclerosis, autism and Parkinson's disease. In my own research, I found abnormal amino acid metabolism, increased imbalance between free radicals and antioxidants in the body, and altered gut microbiomes among some patients with autism spectrum disorder.

What steps can be taken to minimize the health risks brought on by climate change?

We must end the destruction of our natural environment, decrease emissions of greenhouse gases and adopt more "green" behavior. With research demonstrating links between the microbiome and autoimmune, inflammatory and neurologic diseases, it is critical that we minimize antimicrobial exposure. This may involve altering guidelines for the prescription of antibiotics by medical professionals. In addition, given that the microbiome is directly impacted by our daily environment it is important to regularly immerse ourselves in nature and familiarize ourselves with biodiverse surroundings.

One million years ago, the extinction of large-bodied plant-eaters changed the trajectory of life on Earth. The disappearance of these large herbivores reshaped plant life, altered fire regimes across Earth's landscapes, and modified biogeochemical cycling in such a way that Earth's climate became slightly colder. A new study out today by Utah State University Assistant Professor of Watershed Sciences, Trisha Atwood, suggests that modern-day megaherbivores (plant-eaters weighing more than 1000 kg) could soon suffer the same fate as their ancient ancestors, with unknown consequences for Earth and all of its inhabitants.

Armed with a dataset of the diets of over 24,500 mammals, birds, and reptiles, Atwood and her team set out to answer the question "Are plant-eaters, meat-eaters, or animals who eat both plants and meat, at the greatest risk of extinction?" Their findings, published in the journal Science Advances, would challenge a two-decade-long perception that meat-eating predators were the most likely group to meet the ire of Earth's six mass extinction.

The results indicate that with over a quarter of the world's modern-day herbivores threatened with extinction, plant eaters have the highest representation of at-risk species in the present day. The study also highlights that this attack on herbivores is not a new phenomenon. Human activities have led to the disproportionate extinction of herbivores compared to predators since at least the late Pleistocene (11,000-50,000 years ago).

"The results were somewhat shocking," said Atwood. "Our highly publicized and fraught relationship with predatory animals such as lions and wolves has led to the unfounded perception that we are losing predators more than any other trophic group."

Using evidence-based science to challenge misconceptions like the one Atwood's team uncovered is essential for getting society on the right track towards addressing future extinctions. Because a species' role in its ecosystem is intricately linked to what it eats, understanding whether predators, herbivores, or omnivores are at the highest risk of extinction helps scientists and society understand what the potential consequences of losing those species are.

Already the consequences of declines in modern herbivores from land-use change and hunting have begun to echo those that occurred on Earth 1 million years ago; alterations to plant life, changes to fire regimes, and disruptions to nutrient cycling. This study highlights that we must redouble our efforts to strategically invest in conservation and management of herbivores to avoid future dramatic changes in the functions arising from animals at the base of global foodwebs.

Although the results of the study indicate that herbivores are the most at-risk group, it is not clear sailing for predators. The study also identified scavengers, which eat the remains of recently deceased animals (e.g., vultures) and animals that primarily eat fish, such as seabirds, as having a heightened risk of extinction.

"Our results enable us to identify specialized diets within the carnivores that are associated with higher extinction risk, and also identify the habitats these species live in," says Edd Hammill an Assistant Professor of Watershed Sciences at Utah State University and co-author of the study. "It would appear that seabirds across the globe suffer disproportionately high levels of extinction"

To better inform conservation actions, the researchers are now wrestling to understand what it is about herbivores, scavengers, and piscivores (animals that consume fish) that make them more susceptible to extinction compared to other animals.

"Documenting a pattern in extinctions is only the first step towards curbing the loss of species," says Atwood. "Our next step is to understand the intricacies of why this pattern is occurring; only then will we really have a chance at stopping these future extinctions."