Culture

New method identifies adaptive mutations in complex evolving populations

RIVERSIDE, Calif. -- A team co-led by a scientist at the University of California, Riverside, has developed a method to study how HIV mutates to escape the immune system in multiple individuals, which could inform HIV vaccine design.

HIV, which can lead to AIDS, evolves rapidly and attacks the body's immune system. Genetic mutations in the virus can prevent it from being eliminated by the immune system. While there is no effective cure for the virus currently available, it can be controlled with medication.

"Understanding the genetic drivers of disease is important in the biomedical sciences," said John P. Barton, an assistant professor of physics and astronomy at UCR, who co-led the study with Matthew R. McKay, a professor of electronic and computer engineering and chemical and biological engineering at the Hong Kong University of Science and Technology. "Being able to identify genomic rearrangements is key to understanding how illnesses occur and how to treat them."

Barton explained that notable examples of genetic drivers of disease include mutations that allow viruses to escape from immune control, while others confer drug resistance to bacteria.

"It can be difficult, however, to differentiate between real, adaptive mutations and random genetic variation," he added. "The new method we developed allows us to identify such mutations in complex evolving populations."

Evolutionary history, he added, contains information about which mutations affect survival and which simply reflect random variation.

"However, it is computationally difficult to extract this information from data," he said. "We used methods from statistical physics to overcome this computational challenge. Our method can be applied generally to evolving populations and is not limited to HIV."

McKay explained the new method provides a means to efficiently infer selection from observations of complex evolutionary histories.

"It enables us to sort out which genetic changes provide an evolutionary advantage from those that offer no advantage or have a deleterious effect," he said. "The method is quite general and could be potentially used to study diverse evolutionary processes, such as the evolution of drug resistance of pathogens and the evolution of cancers. The accuracy and high efficiency of our approach enable the analysis of selection in complex evolutionary systems that were beyond the reach of existing methods."

Some well-known diseases that have known genetic causes are cystic fibrosis, sickle cell anemia, Duchenne muscular dystrophy, colorblindness, and Huntington's disease.

"In the case of HIV, an understanding of the genetic mutations that lead to HIV resistance could help researchers determine the most appropriate treatment for patients," Barton said. "Our approach isn't limited to HIV, but there are a few reasons why we focused on HIV as a test system. HIV is highly mutable and genetically diverse. It also mutates within humans to escape from the immune system. Understanding the details of how HIV evolves could therefore help to develop better treatments against the virus."

Barton was supported by a grant from the National Institutes of Health. Study results appear in Nature Biotechnology. The title of the research paper is "MPL resolves genetic linkage in fitness inference from complex evolutionary histories."

Barton and McKay were joined in the study by Muhammad Saqib Sohail and Raymond H. Y. Louie of Hong Kong University of Science and Technology and the University of New South Wales.

The University of California, Riverside (http://www.ucr.edu) is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 24,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of almost $2 billion. To learn more, email news@ucr.edu.

Credit: 
University of California - Riverside

Earthquake scenario for large German city

image: City of Cologne: probabilities of occurrence of no (left), weak (middle), or strong (right) damage per building. Of the estimated 170,000 residential buildings in the city, we estimate that more than 10,000 could suffer moderate to severe building damage.

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GFZ

What if there is a major earthquake near Cologne? This scenario is the subject of the "Risk Analysis in Civil Protection 2019", whose report was recently submitted to the German Bundestag (document: Bundestag Drucksache 19/23825). In the 125-page document, a group of experts has listed in detail, on the basis of extensive research work, what effects can be expected in the event of strong ground movements. What Germans usually only know from TV and media reports from other countries is the result of a modeling of a strong earthquake near the megacity of Cologne: ground shaking, damaged and destroyed houses, blocked roads, many injured and dead.

The German Research Center for Geosciences GFZ and its researchers played a central role in this analysis. The GFZ had the task of modeling the ground movements caused by such an earthquake and quantifying possible damage to the city's buildings. In particular, new geophysical models for the Lower Rhine Bay were developed to estimate the influence of the near-surface layers of the subsoil on ground movements. The researchers created a "building-by-building" model of the city in order to quantify the number and vulnerability of buildings that could be affected by the earthquake.

A massive earthquake in the Lower Rhine Bay with a magnitude of 6.5, as assumed for the underlying scenario, is quite possible. The GFZ expert for historical earthquakes, Gottfried Grünthal, says: "Statistical analyses show that an earthquake with a magnitude of 5.5 is to be expected in the Lower Rhine Bay approximately every hundred to three hundred years. A quake with a magnitude of 6.5 is to be expected approximately every 1000 to 3000 years.

Marco Pilz, scientist of the GFZ section earthquake hazard and dynamic risks, describes the fictitious initial situation: "At a depth of only a few kilometers, a tectonic fault ruptures in the Lower Rhine Bay. Only seconds later the shock waves reach the surface and the nearby city of Cologne. The ground starts to shake, buildings creak and sometimes collapse, streets are blocked by falling debris. Good knowledge of the local underground conditions has shown us that these conditions must be taken into account for an accurate modeling of the shaking".

Based on this, a building-related damage assessment suggests that major impacts can be expected in the city of Cologne. "Old buildings are likely to be particularly affected, so that the distribution of damage in the city area could be quite heterogeneous," adds Cecilia Nievas, a researcher from the same section. "Of the estimated 170,000 residential buildings in the city, more than 10,000 could suffer moderate to severe damage according to our calculations".

The further effects, for example on utilities, are more difficult to assess and require detailed investigations: How many hospitals are affected, what capacities remain for the treatment of the injured, and how well do emergency services reach affected regions? GFZ-researcher Pilz: "Although we at GFZ had contributed a large part to this risk analysis, what was remarkable about the cooperation was the involvement of many experts from federal and state authorities, the district government, the affected districts, the cities and their immediately affected services such as the fire department, THW, railroads and energy suppliers. Everyone has worked together, from the very top down to the local level".

Section head Fabrice Cotton adds: "It was a very productive exchange of information. The elaboration of such scenarios is important because they provide an effective tool for dialogue with the authorities and for understanding their needs when planning relief operations. Such exercises can also help to gain a complete overview of the entire seismic risk chain (from the physics of the earthquake to its effects) and to work at the interface between different scientific disciplines (e.g. here between seismology and civil engineering)".

Credit: 
GFZ GeoForschungsZentrum Potsdam, Helmholtz Centre

Research unlocks new information about reading through visual dictionary in the brain

image: Nitin Tandon, MD, and his research team identified a crucial region in the temporal lobe which appears to act as the brain's visual dictionary.

Image: 
James LaCombe

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

These findings were published today in Nature Human Behavior.

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

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

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

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

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

Credit: 
University of Texas Health Science Center at Houston

Report assesses promises and pitfalls of private investment in conservation

image: A shade-grown coffee farm near the town of Jardín in the Antioquia department of Colombia. Coffee beans grown under trees are higher quality, supporting the livelihoods of farmers and their families. Trees on shade-coffee farms are beneficial for soil health and provide habitat to migratory birds. Photo courtesy of Amanda Rodewald.

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Amanda Rodewald

The Ecological Society of America (ESA) today released a report entitled "Innovative Finance for Conservation: Roles for Ecologists and Practitioners" that offers guidelines for developing standardized, ethical and effective conservation finance projects.

Public and philanthropic sources currently supply most of the funds for protecting and conserving species and ecosystems. However, the private sector is now driving demand for market-based mechanisms that support conservation projects with positive environmental, social and financial returns. Examples of projects that can support this triple bottom line include green infrastructure for stormwater management, clean transport projects and sustainable production of food and fiber products.

"The reality is that public and philanthropic funds are insufficient to meet the challenge to conserve the world's biodiversity," said Garvin Professor and Senior Director of Conservation Science at Cornell University Amanda Rodewald, the report's lead author. "Private investments represent a new path forward both because of their enormous growth potential and their ability to be flexibly adapted to a wide variety of social and ecological contexts."

Today's report examines the legal, social and ethical issues associated with innovative conservation finance and offers resources and guidelines for increasing private capital commitments to conservation. It also identifies priority actions that individuals and organizations working in conservation finance will need to adopt in order to "mainstream" the field.

One priority action is to standardize the metrics that allow practitioners to compare and evaluate projects. While the financial services and investment sectors regularly employ standardized indicators of financial risk and return, it is more difficult to apply such indicators to conservation projects. Under certain conservation financing models, for example, returns on investment are partially determined by whether the conservation project is successful - but "success" can be difficult to quantify when it is defined by complex social or environmental changes, such as whether a bird species is more or less at risk of going extinct as a result of a conservation project.

Another priority action is to establish safeguards and ethical standards for involving local stakeholders, including Indigenous communities. In the absence of robust accountability and transparency measures, mobilizing private capital in conservation can result in unjust land grabs or in unscrupulous investments where profits flow disproportionately to wealthy or powerful figures. The report offers guidelines for ensuring that conservation financing improves the prosperity of local communities.

According to co-author Peter Arcese, a professor at the University of British Columbia and adjunct professor at Cornell University, opportunities in conservation finance are growing for patient investors who are interested in generating modest returns while simultaneously supporting sustainable development.

"Almost all landowners I've worked with in Africa and North and South America share a deep desire to maintain or enhance the environmental, cultural and aesthetic values of the ecosystems their land supports," Arcese said. "By creating markets and stimulating investment in climate mitigation, and forest, water and biodiversity conservation projects, we can offer landowners alternative income sources and measurably slow habitat loss and degradation."

Rodewald sees a similar landscape of interest and opportunity. "No matter the system - be it a coffee plantation in the Andes, a timber harvest in the Pacific Northwest, or a farm in the Great Plains - I am reminded again and again that conservation is most successful when we safeguard the health and well-being of local communities. Private investments can be powerful tools to do just that," said Rodewald.

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Ecological Society of America

App predicts risk of developing Alzheimer's

A new study from Lund University in Sweden shows that validated biomarkers can reveal an individual's risk of developing Alzheimer's disease. Using a model that combines the levels of two specific proteins in the blood of those with mild memory impairment, the researchers are able to predict the risk of developing Alzheimer's. The researchers have also developed an app that doctors can use to give patients a risk assessment.

Oskar Hansson and his colleagues have been researching different biomarkers for a long time to produce better diagnostics at an early stage of Alzheimer's disease. Over the past year, they have also developed accurate markers in blood tests for Alzheimer's. The aim has been to identify the disease at an early stage of its progression, before the actual dementia stage, in order to begin treatment to ease symptoms, avoid unnecessary examinations and create a sense of security among patients.

"Many people with Alzheimer's disease currently seek care when they have only developed mild memory impairment, meaning many years before the dementia stage of the disease. It is often difficult for doctors to give the correct diagnosis in people with milder memory impairment, as many different conditions other than Alzheimer's can be the cause. In this study we developed a model that is based on the results of a simple blood test and that with a high degree of validity can predict who will develop Alzheimer's dementia within four years", explains Oskar Hansson, professor in neurology at Lund University and consultant at the clinical memory research unit at Skåne University Hospital.

Among the many biomarkers the researchers have investigated over the years, the current study shows that a model combining the concentration and levels of the two proteins 'phosphorylated tau' and 'neurofilamet light' in the blood is the one that gives the most reliable result and prognosis comparable to today's cerebral spinal fluid (CSF) analyses. The model also provides a more reliable answer than the current basic model involving age, gender, education and basic memory tests.

"In addition to this initial evaluation, the methods that are currently on offer for diagnosing Alzheimer's disease are costly and time-consuming methods using PET cameras and CSF analyses, which are only available in certain specialist healthcare settings. Our goal over the last few years has been to find simple methods that can be used in primary care to make an early diagnosis and to begin treatment to relieve symptoms at an earlier stage. This will require more studies, but we have absolutely come one major step closer to our goal", adds Hansson.

The researchers have also developed an online tool - an app - that combines basic data (age, gender, education and basic cognition tests) with results from the individual's biomarkers in the blood. Taken together, these provide information about an individual patient's risk of developing Alzheimer's disease within two or four years. The app is currently only intended for research and must be validated in more studies before it can be used in healthcare. The app is available at: https://brainapps.shinyapps.io/plasmaatnapp/

The study involved a total of 573 people with mild cognitive impairment and an average age of 71. The participants, who represented a selection of individuals, came from the two major multi-centre studies: the Swedish BioFinder Study and ADNI, the Alzheimer's Disease Neuroimaging Initiative. The study was led by Oskar Hansson and Niklas Mattsson-Carlgren from Lund University and is a collaboration with Henrik Zetterberg and Kaj Blennow at the Sahlgrenska Academy and Sahlgrenska University Hospital, the Clinical Neurochemistry Laboratory in Mölndal and the American pharmaceutical company Eli Lilly, among others.

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Lund University

Study reveals new findings on nature's UV sunscreens

image: New research provides an insight into the behaviour of mycosporine-like amino acids which protect living organisms in our oceans and lakes from the damaging effects of ultraviolet radiation.

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Swansea University

Swansea University research has provided a new insight into the behaviour of nature's own UV sunscreens when they are exposed to other parts of the light spectrum.

Mycosporine-like amino acids (MAAs) provide screening against the damaging effects of ultraviolet radiation in living organisms in our oceans and lakes.

These compounds are known to increase in the environment where levels of UV are high. The uniqueness of these compounds has led to interest from the healthcare industry in the development of more natural sunscreen formulations.

But a new study by scientists at Swansea University has found that these compounds are also increased when living cells of algae are exposed to light at the far-red end of the light spectrum.

Whilst it is widely known that UV light increases the concentrations of MAAs no-one had investigated the effects of other regions of the light spectrum.

The study's author Professor Carole Llewellyn, from the Faculty of Engineering and Science, said: "It is interesting that the far-red light plays a role in the production of these UV sunscreen compounds and highlights how different regions of the light spectrum play an important role in maintaining a healthy balance within cells" .

"Our discovery also highlights the complex interplay in nature and throws into question the role of these sunscreen compounds with the possibility that that they could also be important in contributing to temperature regulation of the earth's surface."

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Swansea University

Study reveals connection between gut bacteria and vitamin D levels

Our gut microbiomes -- the many bacteria, viruses and other microbes living in our digestive tracts -- play important roles in our health and risk for disease in ways that are only beginning to be recognized.

University of California San Diego researchers and collaborators recently demonstrated in older men that the makeup of a person's gut microbiome is linked to their levels of active vitamin D, a hormone important for bone health and immunity.

The study, published November 26, 2020 in Nature Communications, also revealed a new understanding of vitamin D and how it's typically measured.

Vitamin D can take several different forms, but standard blood tests detect only one, an inactive precursor that can be stored by the body. To use vitamin D, the body must metabolize the precursor into an active form.

"We were surprised to find that microbiome diversity -- the variety of bacteria types in a person's gut -- was closely associated with active vitamin D, but not the precursor form," said senior author Deborah Kado, MD, director of the Osteoporosis Clinic at UC San Diego Health. "Greater gut microbiome diversity is thought to be associated with better health in general."

Kado led the study for the National Institute on Aging-funded Osteoporotic Fractures in Men (MrOS) Study Research Group, a large, multi-site effort that started in 2000. She teamed up with Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, and co-first authors Robert L. Thomas, MD, PhD, fellow in the Division of Endocrinology at UC San Diego School of Medicine, and Serene Lingjing Jiang, graduate student in the Biostatistics Program at Herbert Wertheim School of Public Health and Human Longevity Sciences.

Multiple studies have suggested that people with low vitamin D levels are at higher risk for cancer, heart disease, worse COVID-19 infections and other diseases. Yet the largest randomized clinical trial to date, with more than 25,000 adults, concluded that taking vitamin D supplements has no effect on health outcomes, including heart disease, cancer or even bone health.

"Our study suggests that might be because these studies measured only the precursor form of vitamin D, rather than active hormone," said Kado, who is also professor at UC San Diego School of Medicine and Herbert Wertheim School of Public Health. "Measures of vitamin D formation and breakdown may be better indicators of underlying health issues, and who might best respond to vitamin D supplementation."

The team analyzed stool and blood samples contributed by 567 men participating in MrOS. The participants live in six cities around the United States, their mean age was 84 and most reported being in good or excellent health. The researchers used a technique called 16s rRNA sequencing to identify and quantify the types of bacteria in each stool sample based on unique genetic identifiers. They used a method known as LC-MSMS to quantify vitamin D metabolites (the precursor, active hormone and the breakdown product) in each participant's blood serum.

In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. Most of those 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain gut lining health.

"Gut microbiomes are really complex and vary a lot from person to person," Jiang said. "When we do find associations, they aren't usually as distinct as we found here."

Because they live in different regions of the U.S., the men in the study are exposed to differing amounts of sunlight, a source of vitamin D. As expected, men who lived in San Diego, California got the most sun, and they also had the most precursor form of vitamin D.

But the team unexpectedly found no correlations between where men lived and their levels of active vitamin D hormone.

"It seems like it doesn't matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store," Kado said. "It matters how well your body is able to metabolize that into active vitamin D, and maybe that's what clinical trials need to measure in order to get a more accurate picture of the vitamin's role in health."

"We often find in medicine that more is not necessarily better," Thomas added. "So in this case, maybe it's not how much vitamin D you supplement with, but how you encourage your body to use it."

Kado pointed out that the study relied on a single snapshot in time of the microbes and vitamin D found in participants' blood and stool, and those factors can fluctuate over time depending on a person's environment, diet, sleep habits, medications and more. According to the team, more studies are needed to better understand the part bacteria play in vitamin D metabolism, and to determine whether intervening at the microbiome level could be used to augment current treatments to improve bone and possibly other health outcomes.

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University of California - San Diego

New tech can get oxygen, fuel from Mars's salty water

image: This illustration shows Jezero Crater -- the landing site of the Mars 2020 Perseverance rover -- as it may have looked billions of years go on Mars, when it was a lake. Vijay Ramani's lab has developed a way to extract hydrogen and oxygen out of the briny water that may remain under the Martian surface.

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NASA/JPL-Caltech

When it comes to water and Mars, there's good news and not-so-good news. The good news: there's water on Mars! The not-so-good news?

There's water on Mars.

The Red Planet is very cold; water that isn't frozen is almost certainly full of salt from the Martian soil, which lowers its freezing temperature.

You can't drink salty water, and the usual method using electricity (electrolysis) to break it down into oxygen (to breathe) and hydrogen (for fuel) requires removing the salt; a cumbersome, costly endeavor in a harsh, dangerous environment.

If oxygen and hydrogen could be directly coerced out of briny water, however, that brine electrolysis process would be much less complicated -- and less expensive.

Engineers at the McKelvey School of Engineering at Washington University in St. Louis have developed a system that does just that. Their research was published today in the Proceedings of the National Academy of Sciences (PNAS).

The research team, led by Vijay Ramani, the Roma B. and Raymond H. Wittcoff Distinguished University Professor in the Department of Energy, Environmental & Chemical Engineering, didn't simply validate its brine electrolysis system under typical terrestrial conditions; the system was examined in a simulated Martian atmosphere at -33 ?F (-36 ?C).

"Our Martian brine electrolyzer radically changes the logistical calculus of missions to Mars and beyond" said Ramani. "This technology is equally useful on Earth where it opens up the oceans as a viable oxygen and fuel source"

In the summer of 2008, NASA's Phoenix Mars Lander "touched and tasted" Martian water, vapors from melted ice dug up by the lander. Since then, the European Space Agency's Mars Express has discovered several underground ponds of water which remain in a liquid state thanks to the presence of magnesium perchlorate -- salt.

In order to live -- even temporarily -- on Mars, not to mention to return to Earth, astronauts will need to manufacture some of the necessities, including water and fuel, on the Red Planet. NASA's Perseverance rover is en-route to Mars now, carrying instruments that will use high-temperature electrolysis. However, the Mars Oxygen In-Situ Resource Utilization Experiment (MOXIE) will be producing oxygen only, from the carbon dioxide in the air.

The system developed in Ramani's lab can produce 25 times more oxygen than MOXIE using the same amount of power. It also produces hydrogen, which could be used to fuel astronauts' trip home.

"Our novel brine electrolyzer incorporates a lead ruthenate pyrochlore anode developed by our team in conjunction with a platinum on carbon cathode" Ramani said. "These carefully designed components coupled with the optimal use of traditional electrochemical engineering principles has yielded this high performance."

The careful design and unique anode allow the system to function without the need for heating or purifying the water source.

"Paradoxically, the dissolved perchlorate in the water, so-called impurities, actually help in an environment like that of Mars," said Shrihari Sankarasubramanian, a research scientist in Ramani's group and joint first author of the paper.

"They prevent the water from freezing," he said, "and also improve the performance of the electrolyzer system by lowering the electrical resistance."

Typically, water electrolyzers use highly purified, deionized water, which adds to the cost of the system. A system that can work with "sub-optimal" or salty water, such as the technology demonstrated by Ramani's team, can significantly enhance the economic value proposition of water electrolyzers everywhere - even right here on planet Earth.

"Having demonstrated these electrolyzers under demanding Martian conditions, we intend to also deploy them under much milder conditions on Earth to utilize brackish or salt water feeds to produce hydrogen and oxygen, for example through seawater electrolysis," said Pralay Gayen, a postdoctoral research associate in Ramani's group and also a joint first author on this study.

Such applications could be useful in the defense realm, creating oxygen on demand in submarines, for example. It could also provide oxygen as we explore uncharted environments closer to home, in the deep sea.

The underlying technologies enabling the brine electrolyzer system are the subject of patent filing through the Office of Technology Management and are available for licensing from the university.

Credit: 
Washington University in St. Louis

Deep-sea volcanoes: Windows into the subsurface

image: Image 2. Deep-sea hydrothermal vent chimneys on Brothers volcano Northwest Caldera Wall. Image courtesy of Anna-Louise Reysenbach, NSF, ROV Jason, and 2018©Woods Hole Oceanographic Institution.

Image: 
Anna-Louise Reysenbach

Hydrothermally-active submarine volcanoes account for much of Earth's volcanism and are mineral-rich biological hotspots, yet very little is known about the dynamics of microbial diversity in these systems. This week in PNAS, Reysenbach and colleagues, show that at one such volcano, Brothers submarine arc volcano, NE of New Zealand, the geological history and subsurface hydrothermal fluid paths testify to the complexity of microbial composition on the seafloor, and also provide insights into how past and present subsurface processes could be imprinted in the microbial diversity.

"Microbes in hot springs everywhere get their energy in part from the geochemistry of the hot water/fluids. It's the same for the Brothers volcano seafloor hot springs. Since both seawater- and magmatic gas-influenced hydrothermal systems coexist at Brothers, we predicted that the microbes in the active magmatic cone sites (IMAGE1) would be very different from those on the caldera wall (IMAGE 2) that are affected largely by modified seawater" said Reysenbach, Professor of Microbiology at Portland State University. But what they did not expect was that there would also be two very different microbial communities in close proximity to each other on the caldera wall.

From recent International Ocean Discovery Program (IODP) drilling and geophysical measurements there is evidence that after the volcanic caldera collapse of the original stratovolcano to form the present-day caldera, the earliest magmatic hydrothermal system became overprinted by a more seawater dominated system. The authors show that one of the caldera communities aligns with microbes from magmatically-influenced hydrothermal vents of the more recent cone that has grown up from the caldera floor. It is likely that a combination of different subsurface mineral assemblages intersected by the circulating hydrothermal fluids help shape distinct microbial communities on the caldera wall.

"Having studied Brothers volcano for 20 years, this work really astounded me because for the first time I could join the dots from magmatic gases and hydrothermal fluids all the way to microbial communities" said coauthor Cornel de Ronde, Principal Scientist at GNS Science, New Zealand.

This study also describes more than 90 new bacterial and archaeal families, and nearly 300 previously unknown genera, highlighting how little we know about the biodiversity in these systems and how the complexity of the subsurface geology may contribute to high microbial biodiversity. Furthermore, these sites comprise many potentially deeply-branching and symbiotic microbes whose prospective study will add to our understanding of the evolution of life on Earth and the interactions shaping subsurface communities.

"I hope this work will encourage others to see that geology, geochemistry and even geophysics can actually go hand-in-glove with microbial studies. You just have to translate the various pieces of information into a language that is understood by all, then you will discover new paradigms", said de Ronde.

Credit: 
Portland State University

Plant-based diet ramps up metabolism, according to new study

A plant-based diet boosts after-meal burn, leads to weight loss, and improves cardiometabolic risk factors in overweight individuals, according to a new randomized control trial published in JAMA Network Open by researchers with the Physicians Committee for Responsible Medicine.

The study randomly assigned participants--who were overweight and had no history of diabetes--to an intervention or control group in a 1:1 ratio. For 16 weeks, participants in the intervention group followed a low-fat, plant-based diet based on fruits, vegetables, whole grains, and legumes with no calorie limit. The control group made no diet changes. Neither group changed exercise or medication routines, unless directed by their personal doctors.

Researchers used indirect calorimetry to measure how many calories participants burned after a standardized meal at both the beginning and end of the study. The plant-based group increased after-meal calorie burn by 18.7%, on average, after 16 weeks. The control group's after-meal burn did not change significantly.

"These findings are groundbreaking for the 160 million Americans struggling with overweight and obesity," says study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. "Over the course of years and decades, burning more calories after every meal can make a significant difference in weight management."

Within just 16 weeks, participants in the plant-based group lowered their body weight by 6.4 kg (about 14 pounds), on average, compared to an insignificant change in the control group. The plant-based group also saw significant drops in fat mass and visceral fat volume--the dangerous fat found around the internal organs.

The researchers also teamed up with Yale University researchers Kitt Petersen, MD, and Gerald Shulman, MD, to track intramyocellular lipid and hepatocellular lipid--the accumulating fat in muscle and liver cells--in a subset of participants using magnetic resonance spectroscopy. Those in the plant-based group reduced the fat inside the liver and muscle cells by 34% and 10%, respectively, while the control group did not experience significant changes. Fat stored in these cells has been linked to insulin resistance and type 2 diabetes.

"When fat builds up in liver and muscle cells, it interferes with insulin's ability to move glucose out from the bloodstream and into the cells," adds Dr. Kahleova. "After just 16 weeks on a low-fat, plant-based diet, study participants reduced the fat in their cells and lowered their chances for developing type 2 diabetes."

The study also offered new insight into the link between fat within the cells and insulin resistance. The plant-based group decreased their fasting plasma insulin concentration by 21.6 pmol/L, decreased insulin resistance, and increased insulin sensitivity--all positive results--while the control group saw no significant changes.

The plant-based group also reduced total and LDL cholesterol by 19.3 mg/dL and 15.5 mg/dL, respectively, with no significant changes in the control group.

"Not only did the plant-based group lose weight, but they experienced cardiometabolic improvements that will reduce their risk for type 2 diabetes, heart disease, and other health problems," says Dr. Kahleova.

"I plan to stay on this diet for good. Not just for 16 weeks, but for life," reports study participant Sam T., who lost 34 pounds and improved his metabolism during the 16-week study. Since the study has concluded, Sam has continued a plant-based diet, reached his goal weight, and began running half-marathons and marathons.

Credit: 
Physicians Committee for Responsible Medicine

'Financial toxicity' of prostate cancer treatment: Radiation therapy has the greatest impact on patient finances

November 30, 2020 - For men with early-stage prostate cancer, choices about initial treatment carry varying risks of "financial toxicity," reports a study in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The cost of cancer care can be high and the financial burden of prostate cancer treatment can be a significant source of stress for men and their families. "Cost of treatment and the associated financial burden could be an important factor in treatment decisions," says Daniel A. Barocas, MD, MPH, associate professor of urology and medicine at Vanderbilt University, Nashville, Tenn. and senior author of this new paper. Financial toxicity is a relatively new term in cancer care and can be defined as "the distress or hardship experienced by patients due to the cost of cancer treatment."

Differences in financial burden of initial treatments for localized prostate cancer

Prostate cancer is one of the most common cancers in men, with an estimated 190,000 new cases being diagnosed this year. Because their cancer has not spread beyond the prostate gland, men with localized disease have a choice of treatment options, including active surveillance, radiation, or surgery.

According to lead author Benjamin V. Stone, MD, "Modern treatments for localized prostate cancer provide comparable outcomes, with high rates of cancer control and patient survival." But do financial burdens differ according to the choice of initial prostate cancer treatment? To find out, Drs. Stone and Barocas and colleagues analyzed data on 2,121 patients from a follow-up study of treatment for localized prostate cancer.

The study included a questionnaire asking about the direct and indirect costs of prostate cancer and its treatment. Financial burdens were compared for patients choosing surgery (radical prostatectomy), external beam radiation therapy (EBRT), or active surveillance. (Other treatment groups were considered too small for analysis.)

In the first six months after prostate cancer treatment, 15 percent of patients said they experienced "a large or very large" burden of treatment costs. The financial burden was highest for patients who underwent EBRT: 11 percent of patients reported burdens consistent with financial toxicity.

Patients choosing surgery had higher initial financial burdens than those choosing active surveillance. However, these two groups were similar after one year. Financial burdens decreased over time: five years after treatment, only one to three percent of patients were still experiencing financial toxicity. After adjustment for other factors, the financial burdens associated with EBRT were up to twice as high as for surgery or active surveillance.

"Our research shows radiation therapy seems to have the highest financial burden for patients with clinically localized prostate cancer, compared to surgery or active surveillance," says Dr. Stone. "However, our study also shows there is a relatively small percentage of patients who experience a large or very large financial burden due to treatment, and the financial burden lessens over time."

Other factors contributing to higher financial burden included: higher-risk prostate cancer, younger age, non-white race, and lower education. "The association of financial burden with socioeconomic factors such as race and education is in line with the results of previous studies in the United States and worldwide," Drs. Stone and Barocas and coauthors write.

"Overall, our follow-up study suggests that radiation therapy has a longer-lasting burden of costs, compared to other initial treatment options for prostate cancer," the researchers conclude. They note some limitations of their study, including a lack of data on patients' income and other financial resources.

It's also unclear why the financial impact of EBRT is larger than for other treatment options. Dr. Stone adds, "Future studies should include data on out-of-pocket treatment costs as well as various types of indirect costs affecting the financial impact of prostate cancer treatment choices."

Credit: 
Wolters Kluwer Health

Mechanism of action of chloroquine/hydroxychloroquine for COVID-19 infection

image: Figure 1 - Cumulative confirmed deaths from Covid19 infection. Credit ourworldindata.org.

Image: 
Dr. Alberto Boretti, Dr. Bimal Banik, Dr. Stefania Castelletto, Bentham Science Publishers

The recent serious outbreak of Covid19 has affected (November 13, 2020) 53,796,098 people worldwide, resulting in 37,555,669 recovered, 1,310,250 deaths (Figure 1), and a large number of open cases. It has required urgent medical treatments for numerous patients. No clinically active vaccines or antiviral agents are available for Covid19. According to several studies, Chloroquine (CQ) and Hydroxychloroquine (HCQ) have shown promises as Covid19 antiviral especially when administered with Azithromycin (AZM). However, there is significant controversy. Many countries are limiting the use of CQ/HCQ, while others are accepting this therapeutical option (Figure 2). The work [1] is addressing the open question if Chloroquine (CQ) and Hydroxychloroquine (HCQ) are helpful in Covid19 infection by analyzing the latest published literature on the subject while applying the scientific method.

Both papers in favor, or against, this therapeutical option are reviewed [1]. Bias by a conflict of interest is also taken into account. The rationale behind this use is clear. CQ/HCQ is effective against Covid19 in-vitro and in-vivo laboratory studies. Therapy in Covid19 infected patients with CQ/HCQ is supported by evidence of trials and field experiences from multiple sources. The relevant works are reviewed. The presence or absence of conflict of interest is weighed against the conclusions. CQ/HCQ has been used with success in mild cases or medium severity cases. No randomized controlled trial has however been conducted to support the safety and efficacy of CQ/HCQ and AZM for Covid19. Prophylaxis with CQ/HCQ is more controversial, but generally not having side effects, and supported by pre-clinical studies. The mechanism of action against Covid19 is unclear. More research is needed to understand the mechanisms of actions CQ/HCQ have against Covid19 infection, and this requires investigations with nanoscale imaging of viral infection of host cells. Most of the published works indicate CQ/HCQ is likely effective against Covid19 infection, almost 100% in prophylaxis and mild to medium severity cases, and 60% in late infection cases. The percentage of positive works is larger if works conducted under a probable conflict of interest are excluded from the list. The result is consistent with the updated analysis provided in [2], [3], that suggests high efficacy of CQ/HCQ in early treatments and lower efficacy and controversial results only for late treatment. Statistically, 100% of early treatment studies are positive, late treatment studies are mixed with 70% positive effects, 78% of pre-exposure prophylaxis studies are positive, and 100% of post-exposure prophylaxis studies also report positive effects [2], [3].

Credit: 
Bentham Science Publishers

Towards accessible healthcare for all in sub-Saharan Africa

Achieving universal access to healthcare is a key development priority and a major target of the UN's Sustainable Development Goal 3. The COVID-19 pandemic has only reinforced this urge. A rapid development and expansion of public, affordable healthcare infrastructure is particularly crucial in sub-Saharan Africa. In the region, communicable diseases are the first cause of death, infant mortality rates are above five percent, and lengthy journeys to healthcare facilities undermine the accessibility to basic healthcare for millions. At least one sixth of the population lives more than two hours away from a public hospital and one in eight people is no less than one hour away from the nearest health centre.

The team of researchers from the RFF-CMCC European Institute on Economics and the Environment (EIEE), Catholic University of Milan, Fondazione Eni Enrico Mattei and Decatab recently published in PNAS - Proceedings of the National Academy of Sciences a study that provides a comprehensive planning-oriented, inequality-focused analysis of different types of healthcare accessibility in sub-Saharan Africa based on a state-of-the-art georeferenced database of public healthcare facilities.

Researchers, among them Soheil Shayegh, scientist at the RFF-CMCC European Institute on Economics and the Environment (EIEE), elaborate a strategy to efficiently abate the measured inequalities based on a geospatial optimisation algorithm which identifies the optimal location of future healthcare facilities of different tiers* based on the projected distribution of the population of each country by 2030 in order to satisfy the conditions of SDG 3 targets.

"We were able to devise a spatial optimization framework to identify the optimal location and required bed capacity of public healthcare facilities in the region to ensure universal accessibility by 2030" explains Giacomo Falchetta, Research Fellow at FEEM and at the Catholic University of Milan and lead author of the study. "The work builds on different high-resolution data sources, the key one coming from the recent release from the World Health Organisation of a comprehensive, georeferenced database on the location of different typologies of public healthcare facilities in sub-Saharan Africa".

"Our methodology and the results of our analysis can inform local policymakers in their assessment and prioritization of healthcare infrastructure", explains Soheil Shayegh, scientist at the RFF-CMCC European Institute on Economics and the Environment (EIEE). "This is particularly relevant to tackle healthcare accessibility inequality, which is not only prominent within and between countries of sub-Saharan Africa, but also relative to the level of service provided by healthcare facilities".?"Optimized location, type, and capacity of each healthcare facility can be explored in an online interactive dashboard" adds Ahmed Hammad, Data Scientist at Decatab and at the Catholic University of Milan.

The results of the analysis suggest that to meet commonly accepted universal healthcare accessibility targets, sub-Saharan African countries will need to build ~6,200 new facilities by 2030. The researchers also estimate that about 2.5 million new hospital beds need to be allocated between new facilities and ~1,100 existing structures that require expansion or densification.

Credit: 
CMCC Foundation - Euro-Mediterranean Center on Climate Change

Recycled concrete could be a sustainable way to keep rubble out of landfi

image: Shahria Alam, co-director of UBC's Green Construction Research and Training Centre and the lead investigator of the study.

Image: 
UBC Okanagan

Results of a new five-year study of recycled concrete show that it performs as well, and in several cases even better, than conventional concrete.

Researchers at UBC Okanagan's School of Engineering conducted side-by-side comparisons of recycled and conventional concrete within two common applications--a building foundation and a municipal sidewalk. They found that the recycled concrete had comparable strength and durability after five years of being in service.

"We live in a world where we are constantly in search of sustainable solutions that remove waste from our landfills," says Shahria Alam, co-director of UBC's Green Construction Research and Training Centre and the lead investigator of the study. "A number of countries around the world have already standardized the use of recycled concrete in structural applications, and we hope our findings will help Canada follow suit."

Waste materials from construction and demolition contribute up to 40 per cent of the world's waste, according to Alam, and in Canada, that waste amounts to nine million tonnes per year.

The researchers tested the compressive strength and durability of recycled concrete compared with conventional concrete.

Concrete is typically composed of fine or coarse aggregate that is bonded together with an adhesive paste. The recycled concrete replaces the natural aggregate for producing new concrete.

"The composition of the recycled concrete gives that product additional flexibility and adaptability," says Alam. "Typically, recycled concrete can be used in retaining walls, roads and sidewalks, but we are seeing a shift towards its increased use in structures."

Within the findings, the researchers discovered that the long-term performance of recycled concrete adequately compared to its conventional form, and experienced no issues over the five years of the study. In fact, the recycled concrete had a higher rate of compressive strength after 28 days of curing while maintaining a greater or equal strength during the period of the research.

The researchers suggest the recycled concrete can be a 100 per cent substitute for non-structural applications.

"As innovations continue in the composition of recycled concrete, we can envision a time in the future where recycle concrete can be a substitute within more structural applications as well."

Credit: 
University of British Columbia Okanagan campus

Hitting the quantum 'sweet spot': Researchers find best position for atom qubits in silicon

image: Atomic-scale image of two interacting donors in silicon

Image: 
CQC2T

Researchers from the Centre of Excellence for Quantum Computation and Communication Technology (CQC2T) working with Silicon Quantum Computing (SQC) have located the 'sweet spot' for positioning qubits in silicon to scale up atom-based quantum processors.

Creating quantum bits, or qubits, by precisely placing phosphorus atoms in silicon - the method pioneered by CQC2T Director Professor Michelle Simmons - is a world-leading approach in the development of a silicon quantum computer.

In the team's research, published today in Nature Communications, precision placement has proven to be essential for developing robust interactions - or coupling - between qubits.

"We've located the optimal position to create reproducible, strong and fast interactions between the qubits," says Professor Sven Rogge, who led the research.

"We need these robust interactions to engineer a multi-qubit processor and, ultimately, a useful quantum computer."

Two-qubit gates - the central building block of a quantum computer - use interactions between pairs of qubits to perform quantum operations. For atom qubits in silicon, previous research has suggested that for certain positions in the silicon crystal, interactions between the qubits contain an oscillatory component that could slow down the gate operations and make them difficult to control.

"For almost two decades, the potential oscillatory nature of the interactions has been predicted to be a challenge for scale-up," Prof. Rogge says.

"Now, through novel measurements of the qubit interactions, we have developed a deep understanding of the nature of these oscillations and propose a strategy of precision placement to make the interaction between the qubits robust. This is a result that many believed was not possible."

Finding the 'sweet spot' in crystal symmetries

The researchers say they've now uncovered that exactly where you place the qubits is essential to creating strong and consistent interactions. This crucial insight has significant implications for the design of large-scale processors.

"Silicon is an anisotropic crystal, which means that the direction the atoms are placed in can significantly influence the interactions between them," says Dr Benoit Voisin, lead author of the research.

"While we already knew about this anisotropy, no one had explored in detail how it could actually be used to mitigate the oscillating interaction strength."

"We found that there is a special angle, or sweet spot, within a particular plane of the silicon crystal where the interaction between the qubits is most resilient. Importantly, this sweet spot is achievable using existing scanning tunnelling microscope (STM) lithography techniques developed at UNSW."

"In the end, both the problem and its solution directly originate from crystal symmetries, so this is a nice twist."

Using a STM, the team are able to map out the atoms' wave function in 2D images and identify their exact spatial location in the silicon crystal - first demonstrated in 2014 with research published in Nature Materials and advanced in a 2016 Nature Nanotechnology paper.

In the latest research, the team used the same STM technique to observe atomic-scale details of the interactions between the coupled atom qubits.

"Using our quantum state imaging technique, we could observe for the first time both the anisotropy in the wavefunction and the interference effect directly in the plane - this was the starting point to understand how this problem plays out," says Dr Voisin.

"We understood that we had to first work out the impact of each of these two ingredients separately, before looking at the full picture to solve the problem - this is how we could find this sweet spot, which is readily compatible with the atomic placement precision offered by our STM lithography technique."

Building a silicon quantum computer atom by atom

UNSW scientists at CQC2T are leading the world in the race to build atom-based quantum computers in silicon. The researchers at CQC2T, and its related commercialisation company SQC, are the only team in the world that have the ability to see the exact position of their qubits in the solid state.

In 2019, the Simmons group reached a major milestone in their precision placement approach - with the team first building the fastest two-qubit gate in silicon by placing two atom qubits close together, and then controllably observing and measuring their spin states in real-time. The research was published in Nature.

Now, with the Rogge team's latest advances, the researchers from CQC2T and SQC are positioned to use these interactions in larger scale systems for scalable processors.

"Being able to observe and precisely place atoms in our silicon chips continues to provide a competitive advantage for fabricating quantum computers in silicon," says Prof. Simmons.

The combined Simmons, Rogge and Rahman teams are working with SQC to build the first useful, commercial quantum computer in silicon. Co-located with CQC2T on the UNSW Sydney campus, SQC's goal is to build the highest quality, most stable quantum processor.

Credit: 
Centre for Quantum Computation & Communication Technology