The new study shows that rhesus macaque monkeys can be prompted to produce neutralizing antibodies against one strain of HIV that resembles the resilient viral form that most commonly infects people, called a Tier 2 virus. The research also provides the first-ever estimate of vaccine-induced neutralizing antibody levels needed to protect against HIV.

“We found that neutralizing antibodies that have been induced by vaccination can protect animals against viruses that look a lot like real-world HIV,” says Dennis Burton, PhD, chair of Scripps Research’s Department of Immunology and Microbiology, and scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID).

Although the vaccine is far from human clinical trials, the study provides proof-of-concept for the HIV vaccine strategy Burton and his colleagues have been developing since the 1990s.

The goal of this strategy is to identify the rare, vulnerable areas on HIV and teach the immune system to make antibodies to attack those areas. Studies led by Scripps Research scientists have shown that the body needs to produce neutralizing antibodies that bind to the virus’s outer envelope protein trimer. To support this idea, scientists found that they could protect animal models from HIV by injecting them with neutralizing antibodies that were produced in the lab.

The challenge then was to get animals to make the neutralizing antibodies themselves. To do this, scientists needed to expose the immune system to the envelope protein trimer, effectively training it how to spot this target and produce the right antibodies against it.

But there was a big problem. The HIV envelope trimer is unstable and tends to fall apart when isolated. How could scientists use it as an ingredient in a vaccine? A breakthrough came in 2013, when scientists genetically engineered a more stable trimer, or SOSIP.

“For the first time, we had something that looked pretty much like the HIV envelope protein trimer,” says Matthias Pauthner, PhD, a research associate at Scripps Research and co-first author of the new study.

The scientists quickly moved forward with designing an experimental HIV vaccine that contained this stable SOSIP trimer. Their goal with the new study was to see if this kind of vaccine could actually protect animals from infection.

The team tested the vaccine in two groups of rhesus macaques. A previous study using the same vaccine had shown that some immunized monkeys naturally developed low neutralizing antibody titers (antibody levels) in their bodies, while others developed high titers following vaccination. From this study, the researchers selected and re-vaccinated six low titer monkeys and six high titer monkeys. They also studied 12 unimmunized primates as their control group.

The primates were then exposed to a form of the virus called SHIV, an engineered simian version of HIV that contains the same envelope trimer as the human virus.

This particular strain of the virus is known as a Tier 2 virus because it has been shown to be hard to neutralize, much like the forms of HIV circulating in the human population.

The researchers found that the vaccination worked in the high titer animals. The monkeys could produce sufficient levels of neutralizing antibodies against the envelope protein trimer to prevent infection.

“Since HIV emerged, this is the first evidence we have of antibody-based protection from a Tier 2 virus following vaccination,” says Pauthner. “One question now is how can we get such high titers into every animal?”

The focus on titers became especially important as the researchers saw HIV protection wane as the high titers fell in the weeks and months following vaccination. In tracking the titers while continuously exposing animals to the virus, the researchers determined the titers needed to keep HIV at bay.

Importantly, the study also showed that neutralizing antibodies, but not other aspects of the immune system, were the key to stopping the virus. Pauthner says this is an important finding, since other labs have focused on the potential for T cells and other immune system defenses to block infection.

Going forward, the scientists are looking to improve the vaccine design for human trials and keep titers high. “There are many immunological tricks that can be explored to make immunity last longer,” says Pauthner.

The researchers are pursuing a strategy to elicit broadly neutralizing antibodies (bnAbs) that can neutralize many strains of HIV, rather than the single strain described in these studies. “This research gives an estimate of the levels of bnAbs that we may need to induce through vaccination in order to protect against HIV globally,” says Burton.

The report “Minute 319 Colorado River Limitrophe and Delta Environmental Flows Monitoring Final Report” was released today by the U.S. Commissioner of the International Boundary and Water Commission Jayne Harkins at the Colorado River Water Users’ Association Annual Conference in Las Vegas.

“This report provides solid scientific information about our restoration efforts. The findings will help us apply environmental water more effectively in the future,” Harkins said.

Karl W. Flessa, UA professor of geosciences and co-chief scientist of the Minute 319 monitoring team, said “We learned that a little bit of water, in the right places, does a lot of environmental good. The report is really a road map for restoration in the delta.”

The report documents the effects of the environmental flows in the delta from the initial release of a pulse of water from March 23 through May 18, 2014, plus subsequent supplemental deliveries of water through December 2017.

The 2014 pulse flow delivered a fraction of the water the pre-1960 spring floods delivered. People from the Sonoran Institute and Pronatura Noroeste cleared two areas of non-native vegetation beforehand. Restauremos el Colorado has since cleared a third site.

The restoration teams hoped reducing competition would allow native plants such as willows and cottonwoods to germinate and grow after the pulse flow.

The teams planted more than 275,000 willows, cottonwoods, mesquite and palo verde trees in three actively managed restoration sites that total 915 acres (370 hectares). Survival rates for the trees range from 75 to 95 percent. Some of the trees are now more than 14 feet (4.2 meters) tall.

“The restoration teams from the Sonoran Institute, Pronatura Noroeste and Restauremos el Colorado are applying what we’ve learned to locate and prepare restoration sites, plant native trees and deliver just the right amount of water at just the right times,” Flessa said.

The diversity and abundance of birds of special conservation concern increased after the pulse flow and remain high in the restoration sites, the researchers write in the report.

In addition, the researchers found the pulse flow recharged groundwater in the delta and showed it was possible to reconnect the Colorado with the Gulf of California.

“The people living in the riverside communities celebrated when the pulse flow briefly restored water to their river,” Flessa said. “Kids splashed in the water, a brass band played under the San Luis Rio Colorado bridge and people picnicked on the riverbank.”

Flessa, Eloise Kendy of The Nature Conservancy, Karen Schlatter of the Sonoran Institute and J. Eliana Rodríguez-Burgueño of the Universidad Autónoma de Baja California compiled and edited the “Minute 319 Colorado River Limitrophe and Delta Environmental Flows Monitoring Final Report” on behalf of the International Boundary and Water Commission.

Minute 319 is the 2012 addition to the 1944 U.S.-Mexico Water Treaty that authorized environmental flows of water into the Colorado River Delta from 2013 to 2017.

The Minute 319 monitoring team included 39 scientists from universities, government agencies and nongovernmental organizations from both Mexico and the U.S., including El Colegio de la Frontera Norte, the Ensenada-based Pronatura Noroeste, Restauremos el Colorado, the National Audubon Society, The Nature Conservancy, the Tucson-based Sonoran Institute, the Universidad Autónoma de Baja California, the University of Arizona, the U.S. Geological Survey and the U.S. Bureau of Reclamation.

Other UA members of the monitoring team are the late Ed Glenn of the UA Department of Soil, Water and Environmental Science, and Martha Gomez-Sapiens and Hector Zamora of the UA Department of Geosciences.

The International Boundary and Water Commission in El Paso, Texas, funded the UA portion of the Minute 319 monitoring program.

The International Boundary and Water Commission and its partners continue with their restoration efforts under Minute 323, an agreement covering a nine-year period through 2026. Minute 323 provides for at least 210,000 acre-feet of water for environmental purposes, $9 million for scientific research and monitoring, and $9 million for restoration projects. The UA’s Flessa is the lead scientist for the science and monitoring effort.

The paper has been published on December 13th, 2018 in the first issue of Open Access Journal Chemical Physics Letters X.

They said, “As Dirac claimed in 1929 when quantum mechanics was established, the exact application of mathematical theories to solve SE leads to equations too complicated to be soluble. In fact, the number of variables to be determined in the Full-CI method grows exponentially against the system size, and it easily runs into astronomical figures such as exponential explosion. For example, the dimension of the Full-CI calculation for benzene molecule C6H6, in which only 42 electrons are involved, amounts to 1044, which are impossible to be dealt with any supercomputers.”

According to the OCU research group, quantum computers can date back to a Feynman’s suggestion in 1982 that the quantum mechanics can be simulated by a computer itself built of quantum mechanical elements which obey quantum mechanical laws. After more than 20 years later, Prof. Aspuru-Guzik, Harvard Univ. (Toronto Univ. since 2018) and coworkers proposed a quantum algorithm capable of calculating the energies of atoms and molecules not exponentially but polynomially against the number of the variables of the systems, making a breakthrough in the field of quantum chemistry on quantum computers.

When Aspuru’s quantum algorithm is applied to the Full-CI calculations on quantum computers, good approximate wave-functions close to the exact wave-functions of SE under study are required, otherwise bad wave-functions need an extreme number of steps of repeated calculations to reach the exact ones, hampering the advantages of quantum computing. This problem becomes extremely serious for any open shell systems, which have many unpaired electrons not participating in chemical bonding. The OCU researchers have tackled this problem, one of the most intractable issues in quantum science, and made a breakthrough in implementing a quantum algorithm generating particular wave-functions termed configuration state functions in polynomial computing time in 2016.

The previously proposed algorithm requires a considerable number of quantum circuit gate operations proportional to the squares of the number of N, which denotes the number of down-spins of the unpaired electrons in the system. Thus, if N increases, the total computing time increases not exponentially but drastically. Additionally, the complexity of the quantum circuits should be reduced for practical usage of the algorithm and quantum programing architecture. A new quantum algorithm exploits germinal spin functions, termed Serber construction, and reduces the number of the gate operations to only 2N, executing parallelism of the quantum gates. The OCU group said, “This is the first example of practical quantum algorithms, which make quantum chemical calculations realizable on quantum computers equipped with a sizable number of qubits. These implementations empower practical applications of quantum chemical calculations on quantum computers in many important fields.”

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When making sense of the massive amount of information packed into an ice core, scientists face a forensic challenge: how best to separate the useful information from the corrupt.

A new paper published in the journal Entropy shows how tools from information theory, a branch of complexity science, can address this challenge by quickly homing in on portions of the data that require further investigation.

“With this kind of data, we have limited opportunities to get it right,” says Joshua Garland, a mathematician at the Santa Fe Institute who works with 68,000 years of data from the West Antarctic Ice Sheet Divide ice Core. “Extracting the ice and processing the data takes hundreds of people, and tons of processing and analysis. Because of resource constraints, replicate cores are rare. “

By the time Garland and his team got ahold of the data, more than 10 years had passed from the initial drilling of the ice core to the publishing of the dataset it contained. The two-mile ice core was extracted over five seasons from 2007-2012, by teams from the multiple universities funded by the National Science Foundation. From the field camp in West Antarctica, the core was packaged, then shipped to the National Science Foundation Ice Core Facility in Colorado, and finally to the University of Colorado. At the Stable Isotope Lab at the Institute of Arctic and Alpine Research, a state-of-the-art processing facility helped scientists pull water isotope records from the ice.

The result is a highly resolved, complex dataset. Compared to previous ice core data, which allowed for analysis every 5 centimeters, the WAIS Divide core permits analysis at millimeter resolution.

“One of the exciting thing about ice core research in the last decade is we’ve developed these lab systems to analyze the ice in high resolution,” says Tyler Jones, a paleoclimatologist at the University of Colorado Boulder. “Quite a while back we were limited in our ability to analyze climate because we couldn’t get enough data points, or if we could it would take too long. These new techniques have given us millions of data points, which is rather difficult to manage and interpret without some new advances in our [data] processing.”

In previous cores, Garland notes that decades, even centuries, were aggregated into a single point. The WAIS data, by contrast, sometimes gives more than forty data points per year. But as scientists move to analyze the data at shorter time scales, even small anomalies can be problematic.

“As fine-grained data becomes available, fine-grained analyses can be performed,” Garland notes. “But it also makes the analysis susceptible to fine-grained anomalies.”

To quickly identify which anomalies require further investigation, the team uses information theoretic techniques to measure how much complexity appears at each point in the time sequence. A sudden spike in the complexity could mean that there was either a major, unexpected climate event, like a super volcano, or that there was an issue in the data or the data processing pipeline.

“This kind of anomaly would be invisible without a highly detailed, fine-grained, point-by-point analysis of the data, which would take a human expert many months to perform,” says Elizabeth Bradley, a computer scientist at the University of Colorado Boulder and External Professor at the Santa Fe Institute. “Even though information theory can’t tell us the underlying cause of an anomaly, we can use these techniques to quickly flag the segments of the data set that should be investigated by paleoclimate experts.”

She compares the ice core dataset to a Google search that returns a million pages. “It’s not that you couldn’t go through those million pages,” Bradley says. “But imagine if you had a technique that could point you toward the ones that were potentially meaningful?” When analyzing large, real-world datasets, information theory can spot differences in the data that signal either a processing error or a significant climate event.

In their Entropy paper, the scientists detail how they used information theory to identify and repair a problematic stretch of data from the original ice core. Their investigation eventually prompted a resampling of the archival ice core — the longest resampling of a high-resolution ice core to date. When that portion of the ice was resampled and reprocessed, the team was able to resolve an anomalous spike in entropy from roughly 5,000 years ago.

“It’s vitally important to get this area right,” Garland notes, “because it contains climate information from the dawn of human civilization.”

“I think climate change is the most pressing problem ever to face humanity, and ice cores are undoubtedly the best record of Earth’s climate going back hundreds of thousands of years,” says Jones. “Information theory helps us sift through the data to make sure what we’re putting out into the world is the absolute best and most certain product we can.”

“We want to call attention to the fact that while the commitments of signatory parties to UN sustainability goals are important and necessary, they’re also overlooking critical conservation challenges,” says lead author and Academy postdoctoral researcher Dr. Hudson Pinheiro. “We want policy leaders to recognize that some targets need to be reassessed and improved in order to optimize the sustainability of the world’s marine ecosystems and make real progress towards averting the biodiversity crisis.”

In their assessment, the team considered the Paris Accords, which includes 17 Sustainable Development Goals (more specifically SDG-14, which deals with ocean issues), and the Aichi Biodiversity Targets (Target 11 to protect 10% of the ocean by 2020). These goals are continually promoted by the UN Convention for Biological Diversity and signatory countries, which most recently convened in Egypt last week.

The team presented challenges and recommendations related to the following areas of conservation priority: marine protected areas, coastal ecosystem management, overfishing, marine pollution, and ocean acidification.

One sustainability target highlighted by the team requires signatory countries to protect 10% of their coastal waters as marine protected areas, or MPAs, by the year 2020. However, many countries are protecting large expanses of ocean that are low-conflict and of little biological diversity — rather than focusing on coastal regions most in need — in order to meet the target.

“Near-shore waters have a greater diversity of species and face more immediate threats from energy extraction, tourism, development, habitat degradation and overfishing,” says Dr. Luiz Rocha, Academy co-leader of the Hope for Reefs initiative, who in a New York Times op-ed last year argued that the establishment of a large, open-ocean MPA in Brazil was well-intentioned but significantly flawed. “If we leave these highly vulnerable and biodiverse places at risk, we’re not really accomplishing the goal of protecting the seas.”

To dissuade countries from protecting large swathes of ocean habitat that favor low-conflict, low-diversity areas, the team recommends dropping the numerical target of protecting 10 percent of a country’s marine territory. Instead, countries should focus on protecting the highest number of species and ecosystem types to better align with end conservation goals.

The team also evaluated sustainability targets that aim to minimize the impacts of ocean acidification on marine ecosystems by slowing greenhouse gas emissions. They note that, in order to reduce fossil fuel consumption to meet these targets, many countries have turned their focus to expanding “clean” energy sectors, like hydroelectricity, that still depend on environmentally polluting practices.

The team supports several adaptive management approaches, including encouraging industry leaders and local governments to promote policies that further marine conservation despite the position of their respective national governments. For example, the California Academy of Sciences became the first major museum to sign onto the Paris Accords last year when the federal government refused to commit, and the states of California and São Paulo are advancing at a much faster pace to reaching targets than their home countries (United States and Brazil).

“Investment in education and outreach is essential,” says Pinheiro. “Now is the time for scientists, managers, and stakeholders to work together to defend marine biodiversity, ecosystem services, and resources that the world depends on. And it starts with a critical re-evaluation of sustainability targets, how they are being met, and how they motivate marine conservation.”

While observing the young star, astronomers led by Dr John Ilee from the University of Leeds discovered it was not in fact one star, but two.

The main object, referred to as MM 1a, is a young massive star surrounded by a rotating disc of gas and dust that was the focus of the scientists’ original investigation.

A faint object, MM 1b, was detected just beyond the disc in orbit around MM 1a. The team believe this is one of the first examples of a “fragmented” disc to be detected around a massive young star.

“Stars form within large clouds of gas and dust in interstellar space,” said Dr Ilee, from the School of Physics and Astronomy at Leeds.

“When these clouds collapse under gravity, they begin to rotate faster, forming a disc around them. In low mass stars like our Sun, it is in these discs that planets can form.”

“In this case, the star and disc we have observed is so massive that, rather than witnessing a planet forming in the disc, we are seeing another star being born.”

By measuring the amount of radiation emitted by the dust, and subtle shifts in the frequency of light emitted by the gas, the researchers were able to calculate the mass of MM 1a and MM 1b.

Their work, published today in the Astrophysical Journal Letters, found MM 1a weighs 40 times the mass of our Sun. The smaller orbiting star MM 1b was calculated to weigh less than half the mass of our Sun.

“Many older massive stars are found with nearby companions,” added Dr Ilee. “But binary stars are often very equal in mass, and so likely formed together as siblings. Finding a young binary system with a mass ratio of 80:1 is very unusual, and suggests an entirely different formation process for both objects.”

The favoured formation process for MM 1b occurs in the outer regions of cold, massive discs. These “gravitationally unstable” discs are unable to hold themselves up against the pull of their own gravity, collapsing into one — or more — fragments.

Dr Duncan Forgan, a co-author from the Centre for Exoplanet Science at the University of St Andrews, added: “I’ve spent most of my career simulating this process to form giant planets around stars like our Sun. To actually see it forming something as large as a star is really exciting.”

The researchers note that newly-discovered young star MM 1b could also be surrounded by its own circumstellar disc, which may have the potential to form planets of its own — but it will need to be quick.

Dr Ilee added: “Stars as massive as MM 1a only live for around a million years before exploding as powerful supernovae, so while MM 1b may have the potential to form its own planetary system in the future, it won’t be around for long.”

The astronomers made this surprising discovery by using a unique new instrument situated high in the Chilean desert — the Atacama Large Millimetre/submillimetre Array (ALMA).

Using the 66 individual dishes of ALMA together in a process called interferometry, the astronomers were able to simulate the power of a single telescope nearly 4km across, allowing them to image the material surrounding the young stars for the first time.

The team have been granted additional observing time with ALMA to further characterise these exciting stellar systems in 2019. The upcoming observations will simulate a telescope that is 16km across — comparable to the area inside of the ring-road surrounding Leeds.

Now, Medical University of Vienna professor Leopold Eckhart and colleagues have performed one of the largest comparative genomic studies to help determine the key molecular and evolutionary origins of mammalian adaptations seen in skin proteins.

In a new study appearing recently in the advanced online edition of the journal Molecular Biology and Evolution, Eckhart’s team homed in on which genes, among the dozens of mammalian keratin genes, are required for living on land or in the sea. The products of these keratin genes assemble to form the girders of the cytoskeleton in skin cells, called keratinocytes, that maintain a tight barrier between the body and the outside world.

“The results of the present study provide important new data on the evolution of keratins that control the mechanical stability of the epidermis, the outermost layer of the skin,” said Eckhart.

In terrestrial mammals, the epidermis depends on different keratins to maintain the barrier to the environment and to regenerate the epidermis if the skin is wounded. The new report proposes that fully aquatic mammals continuously use the epidermal regeneration program and therefore require only one of the two sets of epidermal keratins.

“It is surprising that the main proteins of the outermost skin layers of terrestrial mammals, including humans, are dispensable in aquatic mammals, such as dolphins, whales, and manatees,” said Eckhart. “And it is remarkable that a stress response program was the starting point of an evolutionary innovation: the new architecture of the epidermis in aquatic mammals.”

The epidermis of dolphins is approximately 50 times thicker than normal human epidermis. Keratins K1, K2, and K10 have been lost and replaced by keratins K6 and K17 in dolphins.

Both the thickening of the epidermis and the key roles of K6 and K17 are also found in human skin wound healing and in lesional skin of patients with psoriasis. In this common skin disease, so-far-unknown genetic factors predispose skin cells to trigger the evolutionarily ancient wound healing program of the epidermis.

“At this point evolutionary biology meets dermatological research, and we hope that this type of ‘translational research’ will yield further insights for the benefit of patients in the future,” said Eckhart.

The research team at the Medical University of Vienna also discovered previously underestimated complexity in the epidermal keratin composition due to so-called “alternative splicing” keratin K10 mRNA and adaptations of keratin gene sets in terrestrial mammals. However, an entire remodeling of the keratin cytoskeleton has occurred only in fully aquatic mammals.

“Our data point to a general pattern of skin evolution: proteins of innermost skin layers are the most conserved, and proteins of the outermost layers are the most diverse,” said Eckhart. “The interactions between keratins and other epidermal proteins need further studies. With progress in comparative genomics and new lines of experimental research, the evolution of the skin will remain an exciting and fruitful research topic.”

The newly discovered ability of the human protein RBBP6 to interfere with Ebola virus replication suggests new ways to fight the infection. As viruses develop and evolve proteins to bypass the body’s immune defenses, human cells in turn develop defense mechanisms against those viruses — an evolutionary arms race that has been ongoing for millions of years. This particular defense mechanism has therapeutic potential, said co-lead author Judd Hultquist, assistant professor of medicine in the division of infectious disease at Northwestern University Feinberg School of Medicine.

“One of the scariest parts about the 2014 Ebola outbreak was that we had no treatments on hand; tens of thousands of people became sick and thousands of people died because we lacked a suitable treatment,” Hultquist said. “What we envision is a small molecule drug that mimics this human protein and could be used in response to an Ebola virus outbreak.”

A small molecule drug is the ultimate goal because these are able to enter cells more easily and, therefore, be more effective.

The study will be published Dec. 13 in the journal Cell. The research was a close collaboration between Hultquist’s lab at Feinberg and labs at Georgia State University and the University of California, San Francisco.

The Ebola virus, like other viruses, invades host cells and uses them to replicate, usurping cellular processes to build viral proteins, which eventually become new copies of the virus. In the current study, Hultquist and his collaborators used mass spectrometry — a technique that identifies specific elements in a sample by mass — to search for interactions between human proteins and Ebola virus proteins. They found strong evidence for an interaction between the Ebola virus protein VP30 and the human protein RBBP6.

Further structural and computational analysis narrowed the interaction down to a small, 23-amino acid-long peptide chain. This small group of amino acids alone is sufficient to disrupt the Ebola virus life cycle, Hultquist said.

“If you take that peptide and put it into human cells, you can block Ebola virus infection,” Hultquist said. “Conversely, when you remove the RBBP6 protein from human cells, Ebola virus replicates much faster.”

Emerging diseases will impact new regions as the world continues to become more interconnected and globalized, Hultquist said. In addition, the looming specter of climate change promises to broaden the reach of vector-borne diseases — by expanding the range of mosquitos, for example — requiring new strategies in curbing disease outbreaks.

Until recently, many diseases in the developing world, including Ebola virus, have been comparatively understudied, Hultquist said.

“It wasn’t until the outbreak of 2014 that other countries started seriously worrying about the potential for a larger epidemic,” Hultquist said. “It’s no longer going to be a local problem that people can afford to ignore. We should be taking a much more proactive stance against some of these neglected viruses and be studying them in real time — so the next time an outbreak does occur, we’re ready for it.”

This work was supported by National Institutes of Health grants P50GM082250, U19AI106754, R01AI120694, P01AI063302, U19AI109664, U19AI109945, P01120943 and R01AI114814.

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