Culture

An intriguing early symptom among some COVID-19 patients is the loss of the sense of smell and/or taste, which has led to the suspicion that the virus that causes the illness, SARS-CoV-2, could be targeting taste buds. But as researchers report in ACS Pharmacology & Translational Science, initial data from mice suggest that might not be the case. 

Viruses cause infection by invading specific cells in the body and reproducing, often damaging or killing those cells in the process. Research has shown that SARS-CoV-2 enters human cells through angiotensin-converting enzyme 2 (ACE2), a receptor on the surface of some cells, including those of the human tongue. Hong-Xiang Liu and colleagues wanted to find out whether ACE2 was expressed specifically in taste bud cells, as well as when this receptor first emerges on tongue cells during fetal development, by studying mice as a model organism. Although the mouse version of ACE2 isn't susceptible to SARS-CoV-2, studying where it's expressed in mice could help clarify what happens when people become infected and lose the sense of taste. 

By analyzing data from oral cells of adult mice, the researchers found that ACE2 was enriched in cells that give the tongue its rough surface, but couldn't be found in most taste bud cells. That means the virus probably does not cause taste loss through direct infection of these cells, the researchers say. Instead, taste buds might be damaged by inflammation caused by the infection. The team also showed that other viruses that affect taste, including the flu virus, might affect different tongue cell types. Further, the researchers analyzed data from oral cells of mice at three developmental stages and found ACE2 in newborn mice but not in fetuses. Previous studies in humans that were not focused on oral cells suggest ACE2 could be expressed at an early fetal stage and then again at a later stage. Therefore, the team states that fetuses could have distinct susceptibilities to SARS-CoV-2 infection at different stages and more work is needed to determine the timing and location of human ACE2 expression.

Astronomers using several telescopes at NOIRLab, including the Southern Astrophysical Research (SOAR) Telescope, have obtained critical data on a particular type of exploding star that produces copious amounts of calcium. The calcium produced in this unique type of supernova explosion is the same calcium found in our bones and teeth and these events account for up to half of the calcium found in the Universe.

Thanks to detailed observations using the SOAR Telescope, located on Cerro Pachón in Chile, and a host of telescopes around the world and in space [1], astronomers have been able to probe the inner workings of a special type of supernova explosion. These particular explosions, from compact stars that lose copious amounts of mass late in their lives, appear to create the element calcium in their last dying gasps — and it is dispersed by the explosion throughout galaxies like the Milky Way. SOAR is a facility of Cerro Tololo Inter-American Observatory (CTIO), a Program of NSF’s NOIRLab.

“Most massive stars create small amounts of calcium during their lifetimes, but events like SN 2019ehk appear to be responsible for producing vast quantities of calcium and in the process of exploding disperse it through interstellar space within galaxies. Ultimately this calcium makes its way into forming planetary systems,” according to Régis Cartier, an astronomer at NOIRLab and a member of the research team, “…and into our bodies in the case of our Earth!”

Raffaella Margutti, senior author of the study at Northwestern University, adds that prior to this event astronomers had only indirect information on these events, called calcium-rich supernovae. “With this direct evidence, we can now confidently rule out the production of calcium-rich supernovae by the vast majority of massive stars,” said Margutti.

“By observing what this star did in its final month before it reached its critical, tumultuous end, we peered into a place previously unexplored, opening new avenues of study,” said Wynn Jacobson-Galan, of Northwestern University, who led the study. The results are published in the 5 August issue of The Astrophysical Journal, which included contributions from a huge collaboration of nearly 70 co-authors from over 15 countries.

The SOAR data were critical to the result. In particular, the infrared spectrum acquired with SOAR, only the second ever obtained of a calcium-rich supernova, opened a new window on the kind of elements expelled by the supernova — elements such as helium, carbon, magnesium and calcium, all of which have a clear spectral fingerprint at infrared wavelengths. Understanding how much and what kind of elements are expelled by a supernova provides critical clues to the nature of the explosion — what kind of star exploded and how it exploded. It also provides insights into how calcium-rich supernovae produce so much calcium. While that interesting question remains an open issue, the SOAR observations represent some of the first steps toward an answer.

“Because these events are so rare, and difficult to detect because they are faint, we don’t have a lot of data on which to base our theories about what happens as these stars expel material in their death throes,” said Cartier.

The explosive event occurred in the relatively nearby galaxy known as Messier 100 which is a popular target for amateur astronomers and is readily visible through small telescopes. In fact, it was amateur astronomer Joel Shepherd who first spotted the light from the exploding star while stargazing in Seattle on 28 April 2019, and soon thereafter it was designated SN 2019ehk. Messier 100 is a beautiful spiral galaxy similar to our Milky Way and is located some 55 million light-years away towards the constellation of Coma Berenices (Berenice’s Hair) in the northern sky near the constellation of Ursa Major (The Great Bear) which contains the Big Dipper.

According to Jacobson-Galan, once the discovery was announced telescopes around the world and in space were pointed at the exploding star.

Augmenting optical and infrared observations like those by SOAR, X-ray observations revealed a flood of high-energy X-rays from SN 2019ehk — the first time they were observed in a calcium-rich supernova. According to the researchers, nobody had ever thought to look at this type of explosion in X-ray light so soon after it occured.

The combination of observations by SOAR and other telescopes led to the team’s conclusion that this calcium-rich supernova was a compact star that expelled an outer layer of gas as it expired. When it exploded its expelled material collided with surrounding material in its outer shell and the extremely hot temperatures produced X-rays and powered the chemical reactions that make calcium.

The SOAR Telescope’s role in studying this event reflects its evolution toward preparations for the massive Legacy Survey of Space and Time (LSST), which will be carried out at the nearby Vera C. Rubin Observatory, also sited on Cerro Pachón. As SOAR Director Jay Elias explained, “The SOAR Telescope is a flexible platform, designed to be able to respond quickly to unexpected astronomical events like this one. In recent years, SOAR has observed many such transient events discovered by large-area surveys in order to probe the nature of those events. We are continually working to increase the telescope’s efficiency and agility as we prepare for the start of LSST.”

“This type of science, which is critically time-dependent, is an important aspect of where astronomy is heading,” said Edward Ajhar of the US National Science Foundation. “Future facilities such as the Rubin Observatory will discover thousands of transient events like this and will keep astronomers busy making many new discoveries.”

Notes

[1] Post-explosion observations and spectra for this result were also collected by several facilities at NOIRLab observatories including the Bok 2.3-meter Telescope at Kitt Peak National Observatory and Las Cumbres Observatory telescopes at CTIO, as well as at the Neil Gehrels Swift Observatory, the Swope 1-meter telescope at Las Campanas Observatory in Chile, the PlaneWave CDK-700 0.7-meter telescope at Thacher Observatory in California, Las Cumbres Observatory telescopes in South Africa (Sutherland), Australia (Siding Spring, Faulkes Telescope South) and the US (McDonald and Faulkes Telescope North), the ATLAS twin 0.5-meter telescope system in Hawai‘i, the Konkoly Observatory in Hungary, the ESO New Technology Telescope, the MMT Observatory, and the Karl G. Jansky Very Large Array in New Mexico. Pre-explosion data from the Hubble Space Telescope, the Spitzer Space Telescope and the Chandra X-Ray Observatory were also used.

More information

This research was presented in a paper to appear in the 5 August issue of The Astrophysical Journal.

The team is composed of  Wynn V. Jacobson-Galán (Northwestern University and University of California, Santa Cruz), Raffaella Margutti (Northwestern University), Charles D. Kilpatrick (University of California, Santa Cruz), Daichi Hiramatsu (University of California, Santa Barbara and Las Cumbres Observatory), Hagai Perets (Technion – Israel Institute of Technology), David Khatami (University of California, Berkeley), Ryan J. Foley (University of California, Santa Cruz), John Raymond (Center for Astrophysics | Harvard & Smithsonian), Sung-Chul Yoon (Seoul National University), Alexey Bobrick (Lund University), Yossef Zenati (Technion – Israel Institute of Technology), Lluís Galbany (Universidad de Granada), Jennifer Andrews (Steward Observatory), Peter J. Brown (Texas A&M University), Régis Cartier (Cerro Tololo Inter-American Observatory/NOIRLab), Deanne L. Coppejans (Northwestern University), Georgios Dimitriadis (University of California, Santa Cruz), Matthew Dobson (Queen’s University Belfast), Aprajita Hajela (Northwestern University), D. Andrew Howell (University of California, Santa Barbara and Las Cumbres Observatory), Hanindyo Kuncarayakti (University of Turku), Danny Milisavljevic (Purdue University), Mohammed Rahman (The Thacher School), César Rojas-Bravo (University of California, Santa Cruz), David J. Sand (Steward Observatory), Joel Shepherd (Seattle Astronomical Society), Stephen J. Smartt (Queen’s University Belfast), Holland Stacey (The Thacher School), Michael Stroh (Northwestern University), Jonathan J. Swift (The Thacher School), Giacomo Terreran (Northwestern University), Jozsef Vinko (CSFK Konkoly Observatory, University of Szeged, and ELTE Eötvös Loránd University), Xiaofeng Wang (Tsinghua University and Beijing Planetarium), Joseph P. Anderson (European Southern Observatory), Edward A. Baron (University of Oklahoma), Edo Berger (Center for Astrophysics | Harvard & Smithsonian), Peter K. Blanchard (Northwestern University), Jamison Burke (University of California, Santa Barbara and Las Cumbres Observatory), David A. Coulter (University of California, Santa Cruz), Lindsay DeMarchi (Northwestern University), James M. DerKacy (University of Oklahoma), Christoffer Fremling (California Institute of Technology), Sebastian Gomez (Center for Astrophysics | Harvard & Smithsonian), Mariusz Gromadzki (University of Warsaw), Griffin Hosseinzadeh (Center for Astrophysics | Harvard & Smithsonian), Daniel Kasen (University of California, Berkeley and Lawrence Berkeley National Laboratory), Levente Kriskovics (CSFK Konkoly Observatory and ELTE Eötvös Loránd University), Curtis McCully (University of California, Santa Barbara and Las Cumbres Observatory), Tomás E. Müller-Bravo (University of Southampton), Matt Nicholl (University of Birmingham and University of Edinburgh), András Ordasi (CSFK Konkoly Observatory), Craig Pellegrino (University of California, Santa Barbara and Las Cumbres Observatory), Anthony L. Piro (The Observatories of the Carnegie Institution for Science), András Pál (CSFK Konkoly Observatory, ELTE Eötvös Loránd University), Juanjuan Ren (National Astronomical Observatory of China), Armin Rest (Space Telescope Science Institute and The Johns Hopkins University), R. Michael Rich (University of California at Los Angeles), Hanna Sai (Tsinghua University), Krisztián Sárneczky (CSFK Konkoly Observatory), Ken J. Shen (University of California, Berkeley), Philip Short (University of Edinburgh), Matthew Siebert (University of California, Santa Cruz), Candice Stauffer (Northwestern University), Róbert Szakáts (CSFK Konkoly Observatory), Xinhan Zhang (Tsinghua University), Jujia Zhang (Yunnan Astronomical Observatory of China), and Kaicheng Zhang (Tsinghua University).

NSF’s National Optical-Infrared Astronomy Research Laboratory (NOIRLab), the US center for ground-based optical-infrared astronomy, operates the international Gemini Observatory (a facility of NSF, NRC–Canada, ANID–Chile, MCTIC–Brazil, MINCyT–Argentina, and KASI–Republic of Korea), Kitt Peak National Observatory (KPNO), Cerro Tololo Inter-American Observatory (CTIO), the Community Science and Data Center (CSDC), and the Vera C. Rubin Observatory. It is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with NSF and is headquartered in Tucson, Arizona. The astronomical community is honored to have the opportunity to conduct astronomical research on Iolkam Du’ag (Kitt Peak) in Arizona, on Maunakea in Hawaiʻi, and on Cerro Tololo and Cerro Pachón in Chile. We recognize and acknowledge the very significant cultural role and reverence that these sites have to the Tohono O’odham Nation, to the Native Hawaiian community, and to the local communities in Chile, respectively.

The Southern Astrophysical Research (SOAR) Telescope, is a joint project of the Ministério da Ciência, Tecnologia e Inovações do Brasil (MCTIC/LNA), NSF’s NOIRLab, the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

The Las Cumbres Observatory global telescope network is a non-profit science institute with the mission of advancing science and education has five telescopes between 0.4 and 1.0 meters deployed at CTIO.

The Bok 2.3-meter Telescope at Kitt Peak National Observatory is operated by Steward Observatory at the University of Arizona.

Links

Research paper
Northwestern University release

Contacts:

Wynn Jacobson-GalanNorthwestern UniversityCell: +1 310-966-7779Email: wynnjacobson-galan2024@u.northwestern.edu

Raffaella MarguttiNorthwestern UniversityCell: +1 857-919-6209Email: raffaella.margutti@northwestern.edu

Régis CartierCTIO/NSF’s NOIRLabCell:+56 982 873 645Email: rcartier@ctio.noao.edu

Peter MichaudNewsTeam ManagerNSF’s NOIRLabGemini Observatory, Hilo HICell: +1 808-936-6643Email: pmichaud@gemini.edu

Amanda KoczPress and Internal Communications OfficerNSF’s NOIRLabCell: +1 626 524 5884Email: akocz@aura-astronomy.org

A Brazilian scientist has produced an inventory of 219 pathogens that infect plants in Brazil, including many agriculturally important species. The annotated list, published in Biota Neotropica, is the largest compilation of information on plant viruses ever produced in Brazil. It presents descriptions of the microorganisms, data on the diseases they cause, and information on their occurrence in native, cultivated and ornamental plants as well as weeds.

“Since the start of my career, I’ve been in the habit of collecting publications on plant viruses in Brazil. I’ve been doing it for decades and have recorded some 8,000 references to date,” said the author, Elliot Watanabe Kitajima, a researcher in the Phytopathology and Nematology Department of the University of São Paulo’s Luiz de Queiroz College of Agriculture (ESALQ-USP).

“I eventually realized that if I were asked how many viruses have been recorded in Brazil, I wouldn’t know the answer, so I drew up an alphabetic list of plant species and of the viruses that naturally infect them. I also produced a reverse list in which the viruses and viroids are followed by the plants infected by each one.”

Viroids are the smallest infectious pathogens known to science, consisting of a short strand of RNA with no protein coating. All known viroids are inhabitants of higher plants, and most cause diseases.

Dr. Kitajima graduated in agronomy from ESALQ-USP in 1958 and earned his PhD in 1967 at the same institution. His résumé includes positions as a researcher at the Agronomic Institute (IAC), an agency of the São Paulo State Government, as a professor at the University of Brasília (UnB) and as a visiting professor at his alma mater, where he retired in 2006 and works as a research collaborator.

The inventory is the outcome of projects conducted under the aegis of the FAPESP Research Program on Biodiversity Characterization, Conservation, Restoration and Sustainable Use (BIOTA-FAPESP).

“This review of the viruses documented between 1926 and 2018 basically sums up everything known about plant viruses in Brazil that infect both spontaneous and cultivated vegetation. The author has produced a most important database that will be both useful to researchers and a relevant pest prevention policy input,” said Carlos Joly, a professor at UNICAMP and a member of BIOTA-FAPESP’s steering committee.

Joly also stressed the importance of the inventory to economic activity. “The list includes 346 plant species belonging to 74 different families and the viruses that naturally infect them. Several viruses are listed for such important crops as the citrus group, for example. Many are well known, but others aren’t. In any event, the occurrence of these pathogens affects fruit production and quality. The ability to recognize them quickly can prevent harm and avoid losses,” Joly said.

Most of the viruses and viroids in the inventory are recognized by the International Committee on Taxonomy of Viruses (ICTV), which authorizes and organizes taxonomic classification and nomenclature. Some of the microorganisms listed have yet to be officially recognized. The list maps the history of pathogenic occurrences in Brazilian agriculture and the evolution of plant virology in Brazil as well as the main centers of research in the field.

For example, citrus tristeza virus (CTV) is one of the top 20 viruses in molecular plant pathology. It causes citrus plants to decline quickly and is the most economically important citrus disease worldwide, being responsible for enormous losses, including the destruction of some 10 million orange trees in the 1940s. This problem was solved on the basis of scientific research, and the state of São Paulo became the world’s largest producer and exporter of industrialized orange juice.

Another important crop pest is bean golden mosaic virus, which emerged in the 1970s, when Brazil was one of the world’s leading producers of beans but had to import the commodity from Mexico owing to the severe losses caused by the disease. Additionally, mosaic is caused in papaya by papaya ringspot virus (PRSV). This disease has wiped out entire plantations in Brazil. Control by roguing (systematic removal of diseased plants) has been sufficiently effective to enable the state of Espírito Santo, which pioneered the technique, to become a major exporter of papaya.

“No viruses can be considered more important than others,” Kitajima said. “Several factors, such as geography, climate, plant species or variety, vectors, and crop practices, will determine how hazardous they are. In monocultures with genetic uniformity, viral diseases can spread very quickly if epidemiological conditions are favorable, causing significant losses. This is a hazard growers must always deal with, and we researchers must also be prepared to offer solutions. To this end, we need appropriate information.”

The article “An annotated list of plant viruses and viroids described in Brazil (1926-2018)” by Elliot Watanabe Kitajima can be read at: doi.org/10.1590/1676-0611-BN-2019-0932.

Journal

Biota Neotropica

DOI

10.1590/1676-0611-bn-2019-0932

Equipped with naloxone and a smartphone app, community members can save lives in the fight against America's opioid crisis, according to a paper from researchers at Drexel University's Dornsife School of Public Health and colleagues published this week in The Lancet journal EClinicalMedicine.

During a pilot study, researchers found that enrolled participants were able to signal and respond to opioid overdoses using a smartphone app, called UnityPhilly, developed by the study team. During 22 overdose emergencies, a participant received an overdose alert on the UnityPhilly app, traveled to the location and then administered naloxone to the overdose victim at the scene. In an additional 52 overdose emergencies, the participant who witnessed the overdose signaled an alert with the app and then administered naloxone themselves. A successful reversal was reported in 95.9% (71/74) of cases. In over half of these events (59.5%), study participants administered naloxone more than five minutes faster than Emergency Medical Services (EMS) were able to arrive on scene.

During the year-long observational study, that concluded in February 2020, 112 adult Philadelphians, 57 of whom use opioids, reported 291 suspected overdoses and alerted nearby volunteers using the UnityPhilly app.

All study participants were trained in how to administer naloxone, use the app and give rescue breathing, and then they were provided with two doses of naloxone. Every time an alert was signaled by pressing an "SOS" button in the app, it also alerted EMS via 911 which allowed them to follow up with their protocol, regardless of whether a layperson responded.

"We know that the lay public is effective at administering naloxone, but now we know that an app can help laypersons provide naloxone faster when every second counts," said senior author Stephen Lankenau, PhD, a professor and associate dean for research at the Dornsife School of Public Health who co-led the study with David Schwartz of Bar-Ilan University, Israel. "By empowering community members with these tools, we strengthen the 'chain of survival,' and keep people alive until EMS or other medical personal administer further aid."

Unless it's reversed in time, an overdose from opioids, such as heroin, or pain relievers, like oxycodone or fentanyl, can cause breathing to slow or stop. Naloxone works as an antagonist that connects to opioid receptors to prevent the effects of other opioids in the body. Signs of an overdose include skin feeling cold, blue nails and lips, slow heartbeat and vomiting, among other symptoms.

In 2018, U.S. overdose deaths decreased for the first time in 25 years with 67,367 drug deaths, roughly seven out of 10 involving opioids, but that rate rose nearly 5% to an estimated 72,000 in 2019, according to the Centers for Disease Control and Prevention. The coronavirus pandemic is also suspected of raising overdose deaths and other "deaths of despair." As of July 15, drug deaths are up 13% this year compared to last year, according to government data compiled by The New York Times.

Philadelphia has the highest per capita overdose mortality rate among large U.S. cities, with 1,150 deaths in 2019, a number up 3% from 2018.

The study focused on four Philadelphia zip codes, with participants recruited in the Kensington neighborhood, which experiences higher drug use and availability of naloxone than other areas of the city. The authors will next look at a city-wide study to test if the app can be scaled for all of Philadelphia.

A survey of Central American migrants traveling through Mexico on their way to the United States found that 74 percent of them experienced a degree of food insecurity, ranging from having only one meal to no food at all for one day or longer. Factors associated with more severe food insecurity include more days in active transit, and the experience of illness by the migrant or their travel companion.

This study by researchers at Columbia University Mailman School of Public Health, School of Public Health of Mexico, and the National Institutes of Public Health in Mexico represents the first attempt to document food insecurity in Central American migrants during their overland transit through Mexico. Their findings are published in the Journal of Immigrant and Minority Health.

The researchers interviewed 95 Central American migrants ages 18 and older traveling overland to the U.S. about their experiences of food insecurity in transit. Interviews took place in a migrant shelter (casa del migrante) in north central Mexico near the midway point of the migrant route through Mexico during the month of July. Respondents were overwhelmingly men (73 percent) and relatively young (mean age of 29, but including youth in their late teens as well as middle aged adults), with the largest proportion from Honduras (58 percent).

Lack of Food

More than a third of respondents (35 percent) said they had gone a day or more with only one meal; 19 percent reported a day or more with no meals; and 20 percent reported two or more consecutive days with no food. Food insecurity may even more pronounced further north, as security conditions worsen in proximity to the U.S. border, contributing to even more challenging access to soup kitchen-like facilities and migrant shelters, the researchers note.

The impact of the severe food insecurity noted, can be both acute potentially affecting health during migration (affecting likelihood of exposure to water borne illness), as well as chronic, potentially impacting life after resettlement. "Lack of access to a reliable food supply during the long travel periods and grueling travel conditions imposed on migrants may increase risk for developing upper respiratory or gastrointestinal infections due to lack of access to a clean water supply. Experiences of food insecurity during the trip may compound risks for later chronic health problems and may negatively impact adaptation post migration," the researchers write.

Importantly, the severity of food insecurity noted was particularly remarkable because the authors documented that migrants had experienced two or more consecutive days with no food at all. Standard scales for documenting food insecurity do not presently capture consecutive days of complete lack of food. The physiologic effect of multiple consecutive days with no food intake would be expected to be severe. Such short-term famine probably occurs frequently during migration in other regions of the world as well, yet data on this is not routinely captured.

Illness

In all, 61 percent of respondents said they had experienced a health issue in the prior two weeks, and 28 percent of this group reported an illness that might impede mobility. One in five respondents (20 percent) reported having a chronic health condition prior to migrating. About one-third (32.6 percent) said they traveled with a companion who was ill in the last two weeks.

A migrant's travel companion could be considered the equivalent of the migrants' social support network during the migration journey, the researchers explain. "The association of the travel companion's illness with severity of food insecurity suggests that migrants share responsibility for acquiring food with their travel companion and thus illness by a member of the travel party can be associated with insecurity of the food supply for the group," they write.

The researchers offer a potential remedy to strengthen migrants' access to food: shelters and healthcare facilities could teach migrants about options for procuring nutrition in the next step of their journey with information on locations of organizations providing meals and pointers for obtaining and prioritizing inexpensive, portable, and nourishing food.

"Understanding the factors associated with relative severity of food insecurity during overland migration can inform strategies for prioritizing assistance and prevention," the authors write.

Background on Central American Migrants

According to the United Nations, in 2017, 70,000 people crossed from Mexico to the US, Primarily from El Salvador, Honduras and Guatemala. During their transit through Mexico, migrants are victims of violence and are also affected by environmental factors that may be life threatening. Other harmful exposures include limited access to health care and basic services including food. Migrants may travel for prolonged periods without finding safe resting stops. In Mexico, faith-based organizations have organized shelters (casas del migrante) located strategically along migration routes to the U.S. where migrants receive lodging, food, medical, and legal assistance.

Recent non-violent deaths at the U.S. Mexican border in migrants without known pre-existing medical conditions have highlighted the dangers of this trip, and suggest that the population reaching the U.S. border may be particularly susceptible to illness potentially because of an acutely undernourished state. In 2019 alone, according to the

International Organization for Migration, 530 migrants died on the U.S.-Mexico border, the vast majority of them Central American migrants. The peak periods for these fatalities appear to be during climate extremes: May through July and December and January, suggesting that food procurement could be particularly challenging.

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.