Culture

Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome. Scientists will now be able to create visualizations of pan-genomes on different scales much more rapidly.

The research article "Dynamic construction in pan-genome structures", was published in De Gruyter's open access journal Open Computer Science.

In order to analyze specific parts of a genome, scientists must be able to "see" the parts they are investigating, and this requires a large amount of processing power and time. The Computational Pan-Genomics Consortium encourages researchers to ensure that all information within a data structure is easily accessible for human eyes by visualization support on different scales. However, a pan-genome graph can have thousands to millions of nodes, which are not very easy for human eyes to visualize.

In an experiment, Dede and Ohlebusch used 10 human genomes and computed a graph that contains part of the large repetitive central exon of the human MUC5AC gene. Formerly, researchers had to create an entire index structure of the genomes, which takes about 8.5 hours and requires 38.5 GB of memory. Using the method developed by Dede and Ohlebusch, the researcher simply has to compute two bit-vectors (on which the construction of the subgraph is based) and the subgraph ? containing the reference path and its ?-neighborhood.

Instead of over eight hours, the software constructed the subgraph (including the computation of the bitvectors, which requires about 10 minutes) in only 24.5 minutes and required 39.6 GB of main memory; the subgraph itself required merely 15 KB of memory.

"Based on solid theory, Dede and Ohlebusch present a new method for the flexible and efficient exploration of suspicious genomic regions, highlighting for example pathogenic genes that distinguish new variants of a virus from all previously known genomes," said Prof. Dr. Jens Stoye, head of the Genome Informatics team, Faculty of Technology, Bielefeld University.

The open access paper can be found here: https://doi.org/10.1515/comp-2020-0018

Quantum computing is increasingly becoming the focus of scientists in fields such as physics and chemistry, and industrialists in the pharmaceutical, airplane, and automobile industries. Globally, research labs at companies like Google and IBM are spending extensive resources on improving quantum computers, and with good reason. Quantum computers use the fundamentals of quantum mechanics to process significantly greater amounts of information much faster than classical computers. It is expected that when error-corrected and fault-tolerant quantum computation is achieved, scientific and technological advancement will occur at an unprecedented scale.

But, building quantum computers for large-scale computation is proving to be a challenge in terms of their architecture. The basic units of a quantum computer are the "quantum bits" or "qubits." These are typically atoms, ions, photons, subatomic particles such as electrons, or even larger elements that simultaneously exist in multiple states, making it possible to obtain several potential outcomes rapidly for large volumes of data. The theoretical requirement for quantum computers is that these are arranged in two-dimensional (2D) arrays, where each qubit is both coupled with its nearest neighbor and connected to the necessary external control lines and devices. When the number of qubits in an array is increased, it becomes difficult to reach qubits in the interior of the array from the edge. The need to solve this problem has so far resulted in complex three-dimensional (3D) wiring systems across multiple planes in which many wires intersect, making their construction a significant engineering challenge.

A group of scientists from Tokyo University of Science, Japan, RIKEN Centre for Emergent Matter Science, Japan, and University of Technology, Sydney, led by Prof Jaw-Shen Tsai, proposes a unique solution to this qubit accessibility problem by modifying the architecture of the qubit array. "Here, we solve this problem and present a modified superconducting micro-architecture that does not require any 3D external line technology and reverts to a completely planar design," they say. This study has been published in the New Journal of Physics.

The scientists began with a qubit square lattice array and stretched out each column in the 2D plane. They then folded each successive column on top of each other, forming a dual one-dimensional array called a "bi-linear" array. This put all qubits on the edge and simplified the arrangement of the required wiring system. The system is also completely in 2D. In this new architecture, some of the inter-qubit wiring--each qubit is also connected to all adjacent qubits in an array--does overlap, but because these are the only overlaps in the wiring, simple local 3D systems such as airbridges at the point of overlap are enough and the system overall remains in 2D. As you can imagine, this simplifies its construction considerably.

The scientists evaluated the feasibility of this new arrangement through numerical and experimental evaluation in which they tested how much of a signal was retained before and after it passed through an airbridge. Results of both evaluations showed that it is possible to build and run this system using existing technology and without any 3D arrangement.

The scientists' experiments also showed them that their architecture solves several problems that plague the 3D structures: they are difficult to construct, there is crosstalk or signal interference between waves transmitted across two wires, and the fragile quantum states of the qubits can degrade. The novel pseudo-2D design reduces the number of times wires cross each other, thereby reducing the crosstalk and consequently increasing the efficiency of the system.

At a time when large labs worldwide are attempting to find ways to build large-scale fault-tolerant quantum computers, the findings of this exciting new study indicate that such computers can be built using existing 2D integrated circuit technology. "The quantum computer is an information device expected to far exceed the capabilities of modern computers," Prof Tsai states. The research journey in this direction has only begun with this study, and Prof Tsai concludes by saying, "We are planning to construct a small-scale circuit to further examine and explore the possibility."

Falling visibility in three major African cities reveals that air pollution has increased significantly over the last 45 years - leaving citizens facing further short-term increases in man-made pollution due to increasing urbanization and economic development, a new study reveals.

Africa is not well-equipped with air quality monitoring, so scientists have used visibility data for capital cities in Ethiopia, Kenya and Uganda as a substitute measurement.

They discovered a significant reduction in visibility since the 1970s, where Nairobi shows the greatest loss (60%), compared to Kampala (56%) and Addis Ababa (34%) - due to increased particulate matter (PM) emissions from vehicles and energy generation.

Correspondingly, PM pollution levels in the three cities are estimated to have increased by 182%, 162% and 62% respectively since the 1970s to the current period.

University of Birmingham experts published their findings in Environmental Research Letters. They are now calling for a systematic approach to understand the causes and effects of air pollution in urban East Africa - allowing improvements in air quality to co-exist with sustainable future economic development.

Report co-author Dr. Ajit Singh commented: "Evidence indicates that ambient air quality in urban African locations is often poor, because of high rates of urbanisation and population growth leading to large-scale construction, increased energy use, vehicle emissions and industrialisation.

"PM air pollution is a major concern in East Africa because of its impact on human health. There are few air quality monitoring networks, resulting in little long-term air quality data, but visibility measured at major cities can be used as a proxy for PM pollution.

"We're tremendously proud of our work in East Africa and the analysis techniques we developed to study Nairobi, Kampala and Addis Ababa are translatable to other parts of the world where air quality data is limited."

The Birmingham team's work is funded by the UK Department for International Development (DFID) through the East Africa Research Fund (EARF) grant 'A Systems Approach to Air Pollution (ASAP) East Africa' and Digital Air Quality (DAQ) - East Africa funded via EPSRC Global Challenges Research Fund.

Co-author Dr. William Avis commented: "Air pollution poses a major health, economic and social threat to cities around the world - inextricably linked to how we plan, manage and live in urban areas. East Africa is no exception to this, but lacks robust air quality data."

Co-author and ASAP lead Professor Francis Pope said: "We need to understand the causes and effects of air pollution in these three cities, which are rapidly developing and will likely experience further increases in PM. Poor air quality acts as a brake on development through increasing expenditure on health, loss of labour productivity, and the impact of illness on education.

"To date, no studies have been able to assess the role of socio-economic factors upon the evolution of air pollution in East Africa. Our work provides data that helps us understand this relationship and provides a much needed baseline for East African urban air quality that can help assess future air quality improvement interventions in the region."

The researchers compared changes in pollution to population growth and GDP statistics - finding increased PM levels linked to increases in national GDP and populations in all three study cities.

They also discovered distinct variations in seasonal visibility, which are largely explained by changing PM sources and sinks in rainy and dry seasons. Visibility was lowest during the dry months and highest in wet months. At all study sites, visibility was higher on Sundays - due to reduced traffic and industrial emissions.

Two specific cell types in the nose have been identified as likely initial infection points for COVID-19 coronavirus. Scientists discovered that goblet and ciliated cells in the nose have high levels of the entry proteins that the COVID-19 virus uses to get into our cells. The identification of these cells by researchers from the Wellcome Sanger Institute, University Medical Centre Groningen, University Cote d'Azur and CNRS, Nice and their collaborators, as part of the Human Cell Atlas Lung Biological Network, could help explain the high transmission rate of COVID-19.

Reported today (23rd April) in Nature Medicine, this first publication with the Lung Biological Network is part of an ongoing international effort to use Human Cell Atlas data to understand infection and disease. It further shows that cells in the eye and some other organs also contain the viral-entry proteins. The study also predicts how a key entry protein is regulated with other immune system genes and reveals potential targets for the development of treatments to reduce transmission.

Novel coronavirus disease - COVID-19 - affects the lungs and airways. Patient's symptoms can be flu-like, including fever, coughing and sore throat, while some people may not experience symptoms but still have transmissible virus. In the worst cases, the virus causes pneumonia that can ultimately lead to death. The virus is thought to be spread through respiratory droplets produced when an infected person coughs or sneezes, and appears to be easily transmitted within affected areas. So far the virus has spread to more than 184 countries and claimed more than 180,000 lives*.

Scientists around the world are trying to understand exactly how the virus spreads, to help prevent transmission and develop a vaccine. While it is known that the virus that causes COVID-19 disease, known as SARS-CoV-2, uses a similar mechanism** to infect our cells as a related coronavirus that caused the 2003 SARS epidemic, the exact cell types involved in the nose had not previously been pinpointed.

To discover which cells could be involved in COVID-19 transmission, researchers analysed multiple Human Cell Atlas§ (HCA) consortium datasets of single cell RNA sequencing, from more than 20 different tissues of non-infected people. These included cells from the lung, nasal cavity, eye, gut, heart, kidney and liver. The researchers looked for which individual cells expressed both of two key entry proteins that are used by the COVID-19 virus to infect our cells.

Dr Waradon Sungnak, the first author on the paper from Wellcome Sanger Institute, said: "We found that the receptor protein - ACE2 - and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose. We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these COVID-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus."

Dr Martijn Nawijn, from the University Medical Center Groningen in the Netherlands, said, on behalf of the HCA Lung Biological Network: "This is the first time these particular cells in the nose have been associated with COVID-19. While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far. The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people."

The two key entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the eye and in the lining of the intestine. This suggests another possible route of infection via the eye and tear ducts, and also revealed a potential for fecal-oral transmission.

When cells are damaged or fighting an infection, various immune genes are activated. The study showed that ACE2 receptor production in the nose cells is probably switched on at the same time as these other immune genes.

The work was carried out as part of the global Human Cell Atlas consortium which aims to create reference maps of all human cells to understand health and disease. More than 1,600 people across 70 countries are involved in the HCA community, and the data is openly available to scientists worldwide.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the HCA Organising Committee, said: "As we're building the Human Cell Atlas it is already being used to understand COVID-19 and identify which of our cells are critical for initial infection and transmission. This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus."

The global HCA Lung Biological Network continues to analyse the data in order to provide further insights into the cells and targets likely to be involved in COVID-19, and to relate them to patient characteristics.

Professor Sir Jeremy Farrar, Director of Wellcome, said: "By pinpointing the exact characteristics of every single cell type, the Human Cell Atlas is helping scientists to diagnose, monitor and treat diseases including COVID-19 in a completely new way. Researchers around the world are working at an unprecedented pace to deepen our understanding of COVID-19, and this new research is testament to this. Collaborating across borders and openly sharing research is crucial to developing effective diagnostics, treatments and vaccines quickly, ensuring no country is left behind."

The Special Turku Coronary Risk Factor Intervention Project (STRIP) of the University of Turku, Finland, examines the benefits of promoting cardiovascular health by dietary counselling from infancy to early adulthood. Altogether 1,116 children and their families from Turku participated in the study starting when the children were 7 months of age.

Half of the children were randomly assigned to a group that received dietary counselling promoting a heart-healthy diet according to the nutritional recommendations. Other half were assigned to the control group who received only the basic health education given at Finnish maternity and child health clinics and school health care. The regular counselling that started in infancy ended when the participants turned 20.

"The research shows that regular dietary counselling starting in infancy has positive impact on the quality of fat in the diet, as well as on the serum cholesterol level, insulin sensitivity, and blood pressure. In addition, the clustering of adverse cardiovascular health markers is less common is the group that participated in the dietary counselling than in the control group", says Assistant Professor and vice principal investigator Katja Pahkala from the University of Turku.

After the dietary counselling aiming at better cardiovascular health ended, the participants were invited to a follow-up study at the age of 26. In 2015-2018, 551 people participated in the follow-up.

"The aim of the study was to investigate whether the persons who participated in the dietary counselling continued to have a more heart-healthy diet and a lower serum cholesterol level than the control group", says Pahkala.

Better cardiovascular health due to counselling

The first results of the follow-up study have now been published demonstrating that the diets of the people in the intervention group continue to be more heart-healthy. In addition, sustained beneficial effects are seen in the serum total and LDL serum cholesterol levels, which are still lower in the intervention than in the control group.

Furthermore, the insulin sensitivity of the persons who participated in the counselling was also better than in the control group.

"As a whole, the results support the idea that counselling on a heart-healthy diet starting in childhood has a positive impact on cardiovascular health, which is sustained after discontinuation of the active counselling", sums Pahkala.

In 1996, palaeontologists found skeletal remains of a giant shark at the northern coast of Spain, near the city Santander. Here, the coast comprises meter high limestone walls that were deposited during the Cretaceous period, around 85 million years ago, when dinosaurs still roamed the world. Scientists from the University of Vienna examined this material now and were able to assign the remains to the extinct shark family, Ptychodontidae, a group that was very specious and successful in the Cretaceous but suddenly vanished mysteriously before the infamous end-Cretaceous extinction event.

Shark vertebrae are rare in the fossil record, but precious

Ptychodontid sharks are mainly known from their teeth, which are flattened and allowed them to crush hard-shelled prey, like bivalves or ammonites, similar to some of today's ray species. However, the find of Spain consists only of parts of the vertebral column and placoid scales (teeth-like scales), which are much rarer than teeth in the fossil record.

In contrast to teeth, shark vertebrae bear important information about a species' life history, such as size, growth and age, which are saved as growth rings inside the vertebra, like in the stem of trees. Statistical methods and the comparison with extant species, allowed the scientists to decode these data and reconstruct the ecology of this enigmatic shark group.

Ptychodontid sharks grew big and old

"Based on the model, we calculated a size of 4-7m and an age of 30 years for the examined shark. Astonishing about this data is the fact that this shark was not yet mature when it died despite its rather old age." states Patrick L. Jambura, lead author of the study. Sharks follow an asymptotic growth curve, meaning that they grow constantly until maturation and after that, the growth curve flattens resulting from a reduced growth rate. "However, this shark doesn't show any signs of flattenings or inflections in the growth profile, meaning that it was not mature, a teenager if you want. This suggests that these sharks even grew much larger (and older)!"

The study suggests that ptychodontid sharks grew very slow, matured very late, but also showed high longevity and reached enormous body sizes. "This might have been a main contributor to their success, but also, eventually, demise."

Do modern sharks face a similar fate?

Many living sharks, like the whale shark or the great white shark, show very similar life history traits, a combination of low recruitment and late maturation, which makes them vulnerable to anthropogenic threats, like overfishing and pollution.

"It might be the case that similar to today's sharks, ptychodontid sharks faced changes in their environment, to which they could not adapt quick enough and, ultimately, led to their demise before even dinosaurs went extinct. However, unlike in the Cretaceous period, it is up to us now, to prevent this from happening to modern sharks again and to save the last survivors of this ancient and charismatic group of fishes!"

Before being halted due to the COVID-19 pandemic, a relentless vaccination campaign had nearly succeeded in eradicating polio from the world. Between 2000 and 2017, the World Health Organization (WHO) estimated that its campaign had reduced the burden of the disease by 99 percent, preventing more than 13 million children from becoming infected and risking potentially debilitating paralysis.

But in recent years, the eradication effort has been plagued by outbreaks of vaccine-derived polio -- in which the weakened virus used in oral polio vaccines evolved the ability to escape from vaccinated individuals and spread in communities with poor vaccination rates.

Now, with support from the Bill and Melinda Gates Foundation, UC San Francisco virologist Raul Andino, PhD and Andrew Macadam, PhD, of the UK's National Institute for Biological Standards and Control (NIBSC) report promising Phase 1 clinical results for the first new oral polio vaccine in 50 years, which they have designed to be incapable of evolving the ability to cause disease in humans.

In a 2017 study, Andino and colleagues discovered that in every vaccine-derived polio outbreak they studied, the virus had used the same three evolutionary steps to mutate from harmless vaccine into a regional menace.

In their new study, published April 23, 2020 in Cell Host and Microbe, Andino, Macadam, and colleagues at the Gates Foundation, the Center for Vaccine Innovation and Access in Seattle, and the Centre for the Evaluation of Vaccination at the University of Antwerp have employed clever genetic wizardry based on decades of study of the poliovirus's biology to redesign the vaccine to ensure that is incapable of following this three-step pathway to re-evolve virulence. Specifically, they stabilized a region of the viral genome that is required for it to re-evolve the ability to infect humans, and ensured that the virus could not get rid of this modification even by exchanging genetic material with related viruses.

"To my knowledge, this is the first effort to rationally design a live attenuated virus based on detailed understanding on its biology, as opposed to the standard approach of blindly passaging the virus in animal cells to eliminate human virulence through poorly understood mechanisms," said Andino, a professor of microbiology and immunology at UCSF.

The new study presents results of a double blinded phase 1 clinical trial conducted in 15 adult volunteers at the University of Antwerp, all of whom had previously been vaccinated with an inactive vaccine composed of shredded virus particles to ensure they could not be made sick by the live vaccine.

The trial found that the new designer polio vaccine was both more stable and more effective than the 50-year old Sabin vaccine from which it was derived. Specifically, the new vaccine caused participants to generate plentiful antibodies against the poliovirus, and despite shedding viral particles in their stool, those particles were unable to infect or cause paralysis in mice. In contrast, previous studies have found that when mice are exposed to viral samples shed by people vaccinated with the standard Sabin oral polio vaccine, as many as 90 percent develop paralysis.

A phase 2 trial is currently underway and shows promise, Andino said, and the WHO is planning a phase 3 trial, hoping to fast-track development of the vaccine as an emergency measure to contain these outbreaks of vaccine-derived polio.

Applying Polio's Lessons to Search for COVID-19 Vaccine

In the wake of the suspension of the WHO's polio eradication efforts during the COVID-19 crisis, Andino's lab is now applying all they've learned designing polio vaccines to the search for new approaches for a SARS-CoV-2 vaccine, including developing a mouse model to better understand exactly how the virus spreads and causes disease.

Dozens of other COVID-19 vaccine efforts are going after the low-hanging fruit of traditional vaccination using isolated viral particles or more advanced RNA-based vaccination, but Andino is working to understand the biological pathways within the virus that might be most amenable to transformation into a safe but effective live attenuated vaccine that could be rapidly produced for worldwide distribution.

"I believe the lesson of polio is that it will take time to develop an optimal vaccine against SARS-CoV-2, and early efforts are likely to meet with unexpected challenges," Andino said. "Once we do have safe and effective vaccines, they'll need to be produced at global scale, which will probably require the use of older technologies that are already in place. Given how little we know about this new coronavirus, I'm betting we'll need all the weapons we can muster."

Historically, pediatric cancer patients have been much more likely than adult cancer patients to enroll in clinical trials as part of their treatment. Now a study by University of Colorado Cancer Center researchers working at Children's Hospital Colorado shows pediatric oncology clinical trial enrollment may be down, from 40-70 percent seen in studies completed in the 1990s, to 20-25 percent in the early 2000s, to 19.9 percent in the current study.

"Childhood cancer is rare overall," says the study's first author, Kelly Faulk, MD, CU Cancer Center investigator and pediatric oncologist at Children's Hospital Colorado, "so historically high enrollment rates to clinical trials has been integral to improving outcomes for our patients."

The study used the Surveillance, Epidemiology, and End Results (SEER) database to estimate the overall number of pediatric cancer cases from 2004-2015, and then compared overall cancer numbers to the number of patients enrolled in clinical trials with the Children's Oncology Group (COG), the largest pediatric oncology cooperative group.

"The potential reduction in enrollment isn't all bad news," says Faulk. "One reason trial enrollment may be decreasing is that good treatments have been developed for some of the most common childhood cancers, thereby shifting the focus and resources toward opening trials for higher risk, but often more rare cancers."

Additionally, pediatric cancers tend to have fewer mutations than adult cancers, offering fewer genetic targets for the kinds of new drugs being tested in many clinical trials. And, Faulk points out, historically low funding for pediatric cancer research limits the ability to open new trials.

Unlike many studies of adult trial enrollment, the current study found no significant racial, ethnic, or socioeconomic disparities within pediatric trial enrollment. Faulk says this highlights the accessibility of COG trials to U.S. patients and also points out that children may be more likely than adult patients to be covered by public insurance options like Medicaid.

However, the study does reveal a group of cancer patients that has historically and continues to under-enroll in clinical trials, namely adolescent and young adult (AYA) patients from ages 15 to twenty-nine.

"They can feel lost between pediatric and adult cancer care, and unfortunately these AYA patients represent a population that has failed to see the same improvements in outcomes that their younger counterparts have," Faulk says. "Given their age and other socioeconomic factors, they may not see doctors as often and commonly suffer from suboptimal health insurance coverage."

To respond to this need, COG trials have increased age eligibility limits on many trials to include patients in this AYA population. Likewise, Faulk would continue to encourage adult cooperative groups to lower their age restrictions to provide more overlap with the upper range of pediatric trials.

"We feel this study is a useful evaluation of pediatric and AYA trial enrollment, representing important shifts in the way we design and test new treatments, and highlighting areas where we can continue to improve our use of clinical trials to give our patients the best possible options," Faulk says.

Philadelphia, April 23, 2020 - The COVID-19 pandemic has resulted in over 2.5 million confirmed cases worldwide and nearly over 170,000 deaths as of April 21 according to the World Health Organization1. Early identification of potential patients and diagnosis followed by isolation are critical for controlling the current pandemic and flattening the curve. This study describes a novel method that may enable decentralized facilities to deliver faster test services for COVID-19 to more people, reports the Journal of Molecular Diagnostics, published by Elsevier.

Diagnostic testing for SARS-CoV-2, the causative viral pathogen of COVID-19, is critical to detecting the virus, understanding its epidemiology, informing case management, and suppressing transmission. Diagnosis currently relies mainly on methods involving RT-qPCR (reverse transcription quantitative PCR), but their capacity is limited by the availability of high-level facilities and instruments.

Lead investigator Jin-Soo Maeng, PhD, Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, and Research Group of Food Processing, Korea Food Research Institute, Wanju-gun, Republic of Korea, and colleagues developed and evaluated RT-LAMP (reverse transcription loop-mediated isothermal amplification) assays to detect genomic RNA (ribonucleic acid) of SARS-CoV-2. RT-LAMP is a one-step nucleic acid amplification method that is used in the diagnosis of infectious diseases caused by bacteria or viruses.

The investigators first designed LAMP primer sets targeting genomic regions specific to SARS-CoV-2 compared to other human pathogenic coronaviruses. Through subsequent screening for sensitivity and reaction time, they found two promising LAMP primer sets. They then optimized RT-LAMP reactions for each of the two sets and evaluated the limit of detection and the specificity to other coronaviruses.

The RT-LAMP assays in this study were able to detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human coronaviruses was not observed. The primer sets were used as the starting point and coupled with crystal violet colorimetric detection, which may increase test throughput. The reaction can be performed and interpreted with a very simple instrument such as a drying oven or water bath. The performance of assays may be further modified by adopting other detection methods and using other enzyme systems.

"Isothermal nucleic acid amplification tests such as RT-LAMP have the potential to be used at the point-of-care with sensitivity comparable to that of the current RT-qPCR tests," noted Dr. Maeng. "Although the proper extraction of sample RNA is still required, our RT-LAMP method has the potential to be run in decentralized test facilities to provide faster test services to more people."

"Although RT-qPCR is the gold standard for detection of pathogens because of their high sensitivity and specificity, there are still some caveats," explained Dr. Maeng. "Centralized testing laboratories, with facilities such as a reliable supply of electricity, expensive instruments, and trained personnel, are required to properly perform RT-qPCR tests. Ideally, screening tests have to be not only sensitive, but also simple and fast so that they can be performed at point-of-care. The main goal of our research was to identify a method with high diagnostic potential that may operate in decentralized facilities."

RT-qPCR measures the amount of a specific RNA, a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. Other molecular assays that detect the pathogen are also in development.

An international team of researchers has put together a new image of Neanderthals based on the genes Neanderthals left in the DNA of modern humans when they had children with them about 50,000 years ago. The researchers found the new pieces of the puzzle by trawling the genomes of more than 27,000 Icelanders. Among other things, they discovered that Neanderthal women gave birth when they were older than the Homo-Sapien women at that time, and Neanderthal men became fathers when they were younger.

It is well-known that a group of our ancestors left Africa and, about 50,000 years ago, met Neanderthals in Europe, and then had children with them.

Now, a new analysis shows that the Neanderthals may have had children with another extinct species of human (Denisovans), before they met Homo Sapiens, and that these children have been fertile and transferred genes from both species further on to modern people.

The analysis also shows that the Neanderthal women living 100,000 - 500,000 years ago on average became mothers at a later age than the contemporary Homo-Sapien women living in Africa. On the other hand, Neanderthal men fathered at a younger age than their Homo-Sapien cousins in Africa.

How can an analysis show all that?

Neanderthals may well be extinct, but small pieces of their DNA live on in us. All living people outside Africa have up to two per cent Neanderthal genes in their DNA.

However, this two per cent is scattered as small fragments in our genomes, and not all individuals have inherited the same fragments. The fragments are like pieces of a jigsaw puzzle, and if they are put together correctly, they will show a picture of the genome in the Neanderthal population that the modern Homo Sapiens had children with.

New method to find the pieces

First, of course, we have to find these pieces. And this is precisely what the group of researchers from Denmark, Iceland and Germany did to produce their results, published today in the scientific journal Nature.

One of them, Laurits Skov, postdoc from the Bioinformatics Research Centre (BiRC) at Aarhus University, has developed a method for tracing Neanderthal fragments in our DNA. Laurits and PhD student Moisès Coll Macià took the method to Iceland, where the genetics firm deCODE has amassed genetic data and health information for more than half of the Icelandic population.

"We spent several months at deCODE in Reykjavik on what can be called field studies for a computational biologist. By combining my method with deCODE's data and expertise, we have analysed 27,566 genomes, and this makes our study 10-times larger than previous studies of Neanderthal genes in human DNA," says Laurits Skov.

Together, the many fragments account for approximately half of a complete Neanderthal genome.

Denisovan genes gone astray?

However, the researchers also found significant fragments of genetic material from another archaic species of human, Denisovans, in the DNA of the Icelanders, and this was something of a surprise. Up to now, Denisovan genes have primarily been found in Australian Aborigines, East Asians and people in Papua New Guinea. So how did these genes end up in Islanders' DNA? And when?

Based on the distribution of genes and mutations, the researchers came up with two possible explanations.

Either Neanderthals had children with Denisovans before they met the Homo Sapiens. This would mean that the Neanderthals with whom Homo Sapiens had children were already hybrids, who transferred both Neanderthal and Denisovan genes to the children.

"Up to now, we believed that the Neanderthals modern people have had children with were "pure" Neanderthals. It's true that researchers have found the remnants of a hybrid between Denisovans and Neanderthals in a cave in East Asia, but we have not known whether there were more of these hybrids and whether, thousands of years later, they had children with modern humans," explains Professor Mikkel Heide Schierup from BiRC.

Or Homo Sapiens met Denisovans long before they met Neanderthals. So far, it has been thought that modern humans met Neanderthals and had children with them first, and not until tens of thousands of years later did they have children with Denisovans.

"Both explanations are equally likely, and both explanations will be scientific news," says Mikkel Heide Schierup.

Neandertal genes of little importance

The study also shows that the Neanderthal DNA has no great importance for modern humans.

"We have previously thought that many of the Neanderthal variants previously been found in modern human DNA were associated with an increased risk of diseases. However, our study shows that the human gene variants located directly beside the Neanderthal genes are better explanations for the risk. We have also found something that can only be explained by Neanderthal genes, but this doesn't mean that much," says Mikkel Heide Schierup.

The properties and risks of diseases that can be linked to Neanderthal DNA are: slightly lower risk of prostate cancer, lower levels of haemoglobin, lower body length (one millimetre) and slightly faster blood plasma clotting.

Under the volcanoes in the Andes where Chile, Argentina and Bolivia meet, there is a gigantic reservoir of molten magma. For several million years, it has been there without fully solidifying or causing a supervolcanic eruption. Geologists have long wondered how this is possible. Researchers from Uppsala University, among others, have now discovered that the secret may be hidden tributaries of hot magma from inside the Earth.

The study is published in the journal Scientific Reports.

"Huge volcanic eruptions from so-called supervolcanoes are very unusual, but when they happen they are extremely devastating. It's incredibly important for volcanologists to clarify what keeps this sleeping giant alive and what can cause it to awaken," says Valentin Troll, Professor of Petrology at the Department of Earth Sciences at Uppsala University.

The giant so-called Altiplano-Puna magma body is estimated to contain 500,000 cubic kilometers of molten and semimolten magma. In order to provide a picture of how much volume is involved, it can be said that the entire island of Gran Canaria would fit inside - more than ten times over. The last really large volcanic eruption here occurred 4 million years ago and was the last in a series of very large explosive eruptions that began 10 million years ago. Some of them can be classified as supervolcanic eruptions.

In order to look for answers as to how the magma could stay molten for millions of years, the researchers studied lavas that were ejected from the magma reservoir during smaller volcanic eruptions after the last major eruption. The chemical composition of such material can provide an indication of how a magma reservoir works, how far down from inside the Earth the material originates, how long it remained in the reservoir and what different processes the magma underwent before it was ejected by the volcano.

In this case, the researchers wants to find out if new magma forces its way into the reservoir and therefore needed to find material that, after forming in the Earth's mantle, was not affected by interaction with the magma that was already in the reservoir.

"This was a demanding task. Under these particular volcanoes in the Central Andes is the Earth's thickest crust, 70 kilometers thick, which means that the magma is given many chances to change and react with the material it comes into contact with when it forces its way up to the surface," says Frances Deegan, a researcher at Uppsala University.

The researchers therefore searched several years for lava that was as "original" as possible. Finally, they found what they were looking for. They have now analyzed the composition of the oxygen isotopes in their samples to find out how lavas were formed and where they originate from. The results showed that the lavas came from deep within the Earth and that they represent the material that feeds the volcanoes of the Central Andes, keeping them alive.

This new knowledge is important to understanding how large, complex volcanoes work.

"Supervolcanic eruptions can cause gigantic disasters. The last one that happened on the Earth was Toba's super eruption in Indonesia 73,000 years ago and it is considered to have almost led to the extinction of mankind. Even if we can't prevent a super eruption from happening, it would be smart to use the time until the next eruption to learn as much as possible to increase the chances for our communities to survive such an event," says Valentin Troll.

BOSTON, MASS. (April 23, 2020) - New research by an international team of scientists reveals that endangered North Atlantic right whales are in much poorer body condition than their counterparts in the southern hemisphere.

This alarming research, led by Dr. Fredrik Christiansen from Aarhus University in Denmark, was published this week in the journal Marine Ecology Progress Series. The study is the result of a collaborative effort by scientist from 12 institutions across 5 nations. Among the coauthors are Senior Scientist Peter Corkeron and Associate Scientist Heather Pettis of the Anderson Cabot Center for Ocean Life at the New England Aquarium and Michael Moore and Carolyn Miller of the Woods Hole Oceanographic Institution.

The analyses revealed that individual North Atlantic right whales--juveniles, adults and mothers--were all in poorer body condition than individual whales from the three populations of Southern right whales. This is alarming, since poor body condition for North Atlantic right whales helps explain why too many of them are dying and why they are not giving birth to enough calves. It could also be affecting their growth and delaying juveniles reaching sexual maturity. These combined impacts on individuals help explain why the species is in decline.

Since the cessation of large-scale commercial whaling in the last century, most populations of southern right whales have recovered well. Now there are about 10,000-15,000 southern right whales. Unfortunately, the same cannot be said for the North Atlantic right whales, found today mostly off the east coast of North America. There are now around 410 individuals left, and the species is heading to extinction. Lethal vessel strikes and entanglement in fishing gear continue to kill these whales. Individual North Atlantic right whales also have to cope with the energetic expense and other costs that are caused by frequent entanglements in fishing gear, in particular lobster and crab pots. These burdens, along with a change in the abundance and distribution of the rice-sized plankton that they eat, have left these whales thin and unhealthy, which makes them less likely to have a calf. This, in turn, contributes to the current overall decline of the species. To quantify "thin and unhealthy," Dr. Christiansen and his colleagues investigated the body condition of individual North Atlantic right whales and compared their condition with individuals from three increasing populations of Southern right whales: off Argentina, Australia and New Zealand.

"Good body condition and abundant fat reserves are crucial for the reproduction of large whales, including right whales, as the animals rely on these energy stores during the breeding season when they are mostly fasting," said Dr. Christiansen. Stored fat reserves are particularly important for mothers, who need the extra energy to support the growth of their newly born calf while they are nursing.

The study is the largest assessment of the body condition of baleen whales in the world. The international research team used drones and a method called aerial photogrammetry to measure the body length and width of individual right whales in these four regions around the world. From aerial photographs, the researchers estimated the body volume of individual whales, which they then used to derive an index of body condition or relative fatness.

"This started out as a conversation between a few of us over dinner at a conference in 2015. Now that the results are out, they're quite shocking," said Peter Corkeron of the Anderson Cabot Center for Ocean Life at the New England Aquarium. "We know that North Atlantic right whales as a species are doing poorly, but this work brings home that as individuals, they're also doing poorly. Their decline has been so rapid that we know it's not simply because not enough calves are being born - too many whales are also dying from human-caused injuries. But this study also shows that their decline isn't solely due to these deaths. Their problems are more insidious, and we need to find a way to ensure that the health of all individual whales improves."

"For North Atlantic right whales as individuals, and as a species, things are going terribly wrong. This comparison with their southern hemisphere relatives shows that most individual North Atlantic right whales are in much worse condition than they should be," said Michael Moore from the Woods Hole Oceanographic Institution. "As a veterinarian, I've long been concerned about how entanglements affect the welfare of these whales. Now we are starting to draw the linkages from welfare to this species' decline. Sub-lethal entanglement trauma, along with changing food supplies is making them too skinny to reproduce well, and lethal entanglement and vessel trauma are killing them. To reverse these changes, we must: redirect vessels away from, and reduce their speed in, right whale habitat; retrieve crab and lobster traps without rope in the water column using available technologies; and minimize ocean noise from its many sources."

This work was supported by funding from NOAA, US Office of Naval Research Marine Mammals Program, World Wildlife Fund for Nature Australia, Murdoch University School of Veterinary and Life Sciences, New Zealand Antarctic Research institute, Otago University and New Zealand Whale and Dolphin Trust and Argentina National Geographic Society.

For 40 years, the New England Aquarium's right whale team has extensively researched and tracked individual right whales and curates the North Atlantic Right Whale Catalog. The scientific team monitors the whales' arrival at breeding and feeding grounds, registering new calves, death rates, and also measuring changes in stress and reproductive hormones.

The Woods Hole Oceanographic Institution is dedicated to advancing knowledge of the ocean and its connection with the Earth system through a sustained commitment to excellence in science, engineering and education, and to the application of this knowledge to problems facing society.

Background

DNA contains the information essential for life. It is therefore critically important to maintain the integrity of DNA. However, due to natural cellular processes and environmental factors, DNA suffers damage at an alarming frequency. To counter this damage, cells have evolved intricate DNA repair processes. One mechanism is known as homologous recombination (HR) and involves the Rad51 protein. Although Rad51 plays a central role in HR, several proteins function to help Rad51. These helper proteins typically form distinct groups that are comprised of multiple subunits.

Overview of Research Achievement

In order to activate Rad51, helper proteins must first attach to Rad51. To study how a helper protein known as Swi5-Sfr1 attaches to Rad51, the YCU team utilized nuclear magnetic resonance spectroscopy. This led to the discovery that two regions within Sfr1 are responsible for anchoring Swi5-Sfr1 to Rad51. Next, by combining purified proteins and purified DNA in a test tube, the Tokyo Tech team demonstrated that mutations in these two regions compromised the activation of Rad51 by Swi5-Sfr1. The researchers reasoned that yeast cells containing mutations in these two regions of Sfr1 would be unable to repair DNA damage, but they were surprised to see that this was not the case. The teams hypothesized that a protein present in the cell but absent from the test tube--which only contains carefully selected purified materials--might be rescuing the DNA repair process. The laboratory of senior author Prof. Hiroshi Iwasaki (Tokyo Tech) had previously shown that there are two HR sub-pathways in yeast: one that relies on Swi5-Sfr1 and another that is dependent on Rad51-related helper proteins. To test whether this other sub-pathway was compensating for the function of mutant Swi5-Sfr1, they made yeast cells lacking Rad51-related helper proteins then re-examined whether mutant Swi5-Sfr1 could promote DNA repair. Remarkably, mutant Swi5-Sfr1 failed to activate Rad51 and cells were unable to repair their DNA. This suggests that the function of the Swi5-Sfr1 helper protein in activating Rad51 is supported by Rad51-related helper proteins.

Future Development

The authors now propose that, rather than functioning independently of each other as was previously thought, Swi5-Sfr1 and the Rad51-related helper proteins collaborate to activate Rad51. "We have seen this collaborative effort between the helper proteins to repair DNA in living cells," says lead author Dr. Bilge Argunhan, a specially appointed assistant professor in Prof. Hiroshi Iwasaki's laboratory. "Now we want to reconstitute the activation of Rad51 in a test tube with both Swi5-Sfr1 and the Rad51-related helper proteins. We believe this approach will be effective in uncovering the finer details involved in this interplay." Some human diseases including several cancers are associated with defects in HR. Since the fundamental mechanisms of HR are evolutionarily conserved from yeast to humans, the authors will combine the powerful genetics that is possible in yeast with biochemical approaches to gain new insights into DNA repair that may be relevant to understanding human disease.

OAK BROOK, Ill. (April 23, 2020) - A special report published today in the journal Radiology outlines prevention, diagnosis and treatment of complications stemming from blood clots in patients with COVID-19. The journal also published two research letters and a case study on this topic.

Clinicians worldwide face this new severe infectious lung disease with no proven therapies. Based on recent reports that demonstrated a strong association between elevated D-dimer levels and poor prognosis, concerns have risen about thrombotic complications in patients with COVID-19.

The National Institute for Public Health of the Netherlands asked a group of radiology and vascular medicine experts to provide guidance for the imaging workup and treatment of these important complications. Their report summarizes evidence for thromboembolic disease and potential diagnostic and preventive actions that can be taken.

"Worldwide, COVID-19 is being treated as a primary pulmonary disease," said Edwin J.R. van Beek, M.D., Ph.D., director at Edinburgh Imaging, Queens Medical Research Institute, at the University of Edinburgh, U.K. "From the analysis of all available current medical, laboratory and imaging data on COVID-19, it became clear that symptoms and diagnostic tests could not be explained by impaired pulmonary ventilation alone."

Recent observations suggest that respiratory failure in COVID-19 is not driven by the development of the acute respiratory distress syndrome alone, but that microvascular thrombotic processes may play a role. This may have important consequences for the diagnostic and therapeutic management of these patients. There is a strong association between D-dimer levels, disease progression and chest CT features suggesting venous thrombosis. In addition, various studies in patients with COVID-19 have shown a very strong association between increased D-dimer levels and severe disease/poor prognosis.

The report authors stress that careful attention needs to be paid to the initial diagnosis and treatment of the prothrombotic and thrombotic state that can occur in a substantial percentage of COVID-19 patients.

"Imaging and pathological investigations confirmed the COVID-19 syndrome is a thrombo-inflammatory process that initially affects lung perfusion, but consecutively affects all organs of the body," Professor van Beek said. "This highly thrombotic syndrome leads to macro-thrombosis and embolism. Therefore, strict thrombosis prophylaxis, close laboratory and appropriate imaging monitoring with early anti-coagulant therapy in case of suspected venous thromboembolism are indicated."

Recommendations for diagnostic and therapeutic management, which vary based on patient symptoms and risk profiles, include prophylactic-dose heparin, chest CT, CT pulmonary angiography and routine D-dimer testing.

Findings have also emerged linking COVID-19 more specifically with pulmonary embolism. A research letter from Hôpitaux Universitaires de Strasbourg published today in Radiology reported that of 106 pulmonary CT angiograms performed for COVID-19 patients over a one-month period in a tertiary care center in France, 32 patients (30%) had acute pulmonary embolus (PE). This rate of PE is much higher than usually encountered in critically ill patients without COVID-19 infection (1.3%,) or in emergency department patients (3 to 10%). In the study, a D-dimer threshold of 2660 μg/L detected all patients with PE on chest CT.

A second research letter published today described a study from Centre Hospitalier Universitaire de Besancon in France pointed to high proportion (23%) of COVID-19 patients with contrast CT had PE. PE was diagnosed at mean of 12 days from symptom onset. Patients with PE were more likely require care in the critical care unit and to require mechanical ventilation.

Lastly, a case report from Cooper University Hospital in Camden, New Jersey, describes multiple areas of pulmonary and arterial thrombosis in an 84-year-old man with COVID-19.

"COVID-19 is more than a lung infection," Professor van Beek said. "It affects the vasculature of the lungs and other organs and has a high thrombosis risk with acute life-threatening events that require adequate treatment with anticoagulants based on laboratory monitoring with appropriate imaging tests as required."

RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources. RSNA's COVID-19 Resources page houses the latest guidance, original research, image collection and more. The page will be updated on an ongoing basis.

Have you ever noticed how a bite of warm cherry pie fills your mouth with sweetness, but that same slice right out of the refrigerator isn't nearly as tempting? Scientists know this phenomenon to be true, but the mechanism behind it has been poorly understood.

Now, using fruit flies as his subjects, UC Santa Barbara Distinguished Professor Craig Montell has discovered one process responsible for this occurrence. Montell's team, which includes Qiaoran Li, Nicolas DeBeaubien and Takaaki Sokabe, found that cool temperatures suppress the appeal of sweetness. However, these conditions did not affect the sugar neurons themselves. Rather, they acted via other sensory cells by way of a protein originally discovered to sense light in the eye. Despite this, the perception of coolness in sugary food is not altered by light. The results appear in the journal Current Biology.

"The appeal of food is influenced by more than just chemical composition," said Montell, the Duggan professor in the Department of Molecular, Cellular, and Developmental Biology. "We already know that cool temperatures reduce the delectability of sweetness in humans." He and his colleagues wondered whether this was also true in fruit flies, and if so, what were the underlying mechanisms?

The team found a significant difference in fruit flies' interest in feeding between 23 degrees Celsius (73.4° Fahrenheit) and 19° C (66.2° F). That said, they measured no difference in the activity of the flies' sweet-sensing taste neurons, despite the change in behavior.

"Since the temperature is not directly affecting the sugar neurons, it must be affecting some other types of cells, which then indirectly affect the propensity to consume sugar," Montell noted.

Fruit flies detect sugar with one type of taste neuron. Bitter is sensed by another type of neuron, and mechanosensory neurons detect the texture of food, such as hardness. However, temperature sensation is not quite as simple. Both bitter and mechanosensory neurons are also involved in detecting coolness. Only if both are activated does the brain interpret that as a cool signal.

All of these stimuli seem to reduce the animal's desire to feed, explained Montell. Bitter compounds trigger bitter neurons, which tell the fly to stop feeding. Hard foods trigger the mechanosensory neurons, which also tell the fly to stop feeding. And cool temperatures trigger both, to the same effect.

Critical to this response is a protein called rhodopsin 6. Rhodopsins are most commonly associated with vision, but over the past few years the Montell group has connected rhodopsins to a variety of other senses. Indeed, just a couple weeks prior, Montell's lab published the first study connecting different members of this class of protein to chemical taste.

"The bitter neurons express this rhodopsin called Rh6, and if you get rid of it, then cool temperatures no longer suppress the appeal of sugar," he said.

Without Rh6, the bitter-and-cool-detecting neurons are no longer turned on by low temperatures. And since cool-sensation requires activating multiple, different types of neurons, loss of Rh6 prevents the fly from recognizing the lower temperature, thereby eliminating the decreased attraction to sugary food.

"The surprise was finding that it was really the other neurons, not the sugar neurons, whose activity went up," Montell said, "and that the cool activation of other neurons was indirectly suppressing the sugar neurons."

The sweet-sensing neurons are still activated by sugars at low temperatures; however, the activation of these other neurons by decreased temperature suppresses the communication between the sweet-detecting neurons and the animal's brain. This is likely achieved by an inhibitory neurotransmitter released by the bitter/cool-activated neurons.

As for why fruit flies avoid food when it's chilly, Montell suspects it's due to their metabolism. Fruit flies' metabolism, and thus food requirements, are affected by temperature. Lower temperatures mean slower metabolisms, and less need for food. And generally, if the food is cold, so is the fly.

In fact, the fly generation time -- the time it takes an egg to turn into an adult fly -- doubles from 10 days to 20 when the temperature is lowered from 25 to 18 degrees Celsius. "Everything is just slowed down," Montell said, "and that's why feeding is reduced. You don't want to eat the same amount when your metabolism is slowed down." This explanation doesn't hold true for warm-blooded animals like humans, even if we show a similar behavior.

In the future, Montell and first author Qiaoran Li plan to further investigate the mechanosensory side of food appeal by looking at how particle size influences feeding behavior. As an example, he offers the distinct difference between fresh and refrozen ice cream. Despite having the same chemical composition and temperature, most people prefer ice cream that hasn't melted and refrozen into a block.

Reflecting on the surprising finding, Montell remarked, "It's great for your expectations to be wrong, as long as you can then figure out what's right."