Brain

Hydride transfer is a prevailing protocol for reduction of unsaturated compounds, which is traditionally accomplished under the catalysis of transition-metals, particularly those of noble metals. Because of concerns associated with their low abundance, high toxicity and harmful transition-metal residues, considerable research has recently focused on the use of main-group organic counterparts as surrogates for conventional metal hydrides.

Recently, N-heterocyclic phosphines (NHPs) have emerged as a new group of promising catalysts for metal-free reductions. Their excellent hydricity of the P-H bond, which rivals or even exceeds those of many metal-based hydrides, is the result of hyperconjugative interactions between the lone-pair electrons on N atoms and the adjacent sigma*(P-H) orbital, as reflected by the resonance structures of the diazaphospholene skeleton. The umpolung reactivities of phosphines derived in this way stimulated researchers to identify innovative structures with comparable or enhanced hydricities. Significant developments in the past decade have made P-H hydrides an attractive research area in main-group hydrides. Many NHPs (Scheme 1) with diverse structures and reactivities have been developed and used as powerful stoichiometric or catalytic reductants in organic syntheses, such as catalytic reduction of polar unsaturated bonds and the hydroboration of pyridines.

Several exhaustive reviews have previously discussed carbon- and borane-based hydrides in terms of their hydridic reactivities and applications in chemical transformations. However, there have been few summaries of up-to-date synthetic applications of N-heterocyclic phosphines, particularly with regard to recent progress in asymmetric chemistry. This review from Jin-Dong Yang and Jin-Pei Cheng's group summarized recent progress in studies of the reactivity and synthetic applications of these phosphorus-based hydrides, with the aim of providing practical information to enable exploitation of their synthetically useful chemistry.

The authors outlined significant advances in this area. In the first section, they described experimental methods for quantifying the thermodynamic and kinetic hydricities of NHPs, along with a brief introduction to the NHP catalytic mechanism. The synthetic uses of NHPs as hydridic catalysts, categorized by the identity of the terminal reductants, were summarized (Scheme 2). Where applicable, the use of measured reactivity parameters to rationalize these catalytic reductions was attempted.

Moreover, the reactions developed in the past mainly focused on the hydridic reduction ability of NHPs. On the basis of recent findings that NHPs can also serve as good hydrogen-atom donors and their corresponding phosphinyl radicals are excellent electron donors. Hence, a brief introduction to recent progress in radical reactions of NHPs was also provided. This alternative pathway might provide a potential route to previously inaccessible reactivity in hydridic reduction. Finally, the authors discussed promising future applications of P-H hydrides in various fields.

London, 30 November 2020 - In a major scientific advance, the latest version of DeepMind's AI system AlphaFold has been recognised as a solution to the 50-year-old grand challenge of protein structure prediction, often referred to as the 'protein folding problem', according to a rigorous independent assessment. This breakthrough could significantly accelerate biological research over the long term, unlocking new possibilities in disease understanding and drug discovery among other fields.

Today, results from CASP14 show that DeepMind's latest AlphaFold system achieves unparalleled levels of accuracy in structure prediction. The system is able to determine highly-accurate structures in a matter of days. CASP, the Critical Assessment of protein Structure Prediction, is a biennial community-run assessment started in 1994, and the gold standard for assessing predictive techniques. Participants must blindly predict the structure of proteins that have only recently - or in some cases not yet - been experimentally determined, and wait for their predictions to be compared to experimental data.

CASP uses the "Global Distance Test (GDT)" metric to assess accuracy, ranging from 0-100. The new AlphaFold system achieves a median score of 92.4 GDT overall across all targets. The system's average error is approximately 1.6 Angstroms - about the width of an atom. According to Professor John Moult, Co-founder and Chair of CASP, a score of around 90 GDT is informally considered to be competitive with results obtained from experimental methods.

Professor John Moult, Co-Founder and Chair of CASP, University of Maryland said:

"We have been stuck on this one problem - how do proteins fold up - for nearly 50 years. To see DeepMind produce a solution for this, having worked personally on this problem for so long and after so many stops and starts wondering if we'd ever get there, is a very special moment."

Why protein structure prediction matters

Proteins are essential to life and their shapes are closely linked with their functions. The ability to predict protein structures accurately enables a better understanding of what they do and how they work. There are currently over 200 million proteins in the main database and only a fraction of their 3D structures have been mapped out.

A major challenge is the astronomical number of ways a protein could theoretically fold before settling into its final 3D structure. Many of the greatest challenges facing society, like developing treatments for diseases or finding enzymes that break down industrial waste, are fundamentally tied to proteins and the role they play. Determining protein shapes and functions is a major field of scientific research, primarily using experimental techniques that can take years of painstaking and laborious work per structure, and require the use of multi-million dollar specialised equipment.

DeepMind's approach to the protein folding problem

This breakthrough builds on DeepMind's first entry at CASP13 in 2018, where the initial version of AlphaFold achieved the highest level of accuracy among all participants. Now, DeepMind has developed new deep learning architectures for CASP14, drawing inspiration from the fields of biology, physics, and machine learning, as well as the work of many scientists in the protein folding field over the past half-century.

A folded protein can be thought of as a "spatial graph", where residues are the nodes and edges connect the residues in close proximity. This graph is important for understanding the physical interactions within proteins, as well as their evolutionary history. For the latest version of AlphaFold used at CASP14, DeepMind created an attention-based neural network system, trained end-to-end, that attempts to interpret the structure of this graph, while reasoning over the implicit graph that it's building. It uses evolutionarily related sequences, multiple sequence alignment (MSA), and a representation of amino acid residue pairs to refine this graph.

By iterating this process, the system develops strong predictions of the underlying physical structure of the protein. Additionally, AlphaFold can predict which parts of each predicted protein structure are reliable using an internal confidence measure.

The system was trained on publicly available data consisting of ~170,000 protein structures from the protein data bank, using a relatively modest amount of compute by modern machine learning standards - approximately 128 TPUv3-cores (roughly equivalent to ~100-200 GPUs) run over a few weeks.

Potential for real world impact

DeepMind is excited to collaborate with others to learn more about AlphaFold's potential, and the AlphaFold team is looking into how protein structure predictions could contribute to understanding of certain diseases with a few specialist groups.

There are also signs that protein structure prediction could be useful in future pandemic response efforts, as one of many tools developed by the scientific community. Earlier this year, DeepMind predicted several protein structures of the SARS-CoV-2 virus, and impressively quick work by experimentalists has now confirmed that AlphaFold achieved a high degree of accuracy on its predictions.

AlphaFold is one of DeepMind's most significant advances to date. But as with all scientific research, there's still much to be done, including figuring out how multiple proteins form complexes, how they interact with DNA, RNA, or small molecules, and how to determine the precise location of all amino acid side chains.

As with its earlier CASP13 AlphaFold system, DeepMind is planning to submit a paper detailing the workings of this system to a peer-reviewed journal in due course, and is simultaneously exploring how best to provide broader access to the system in a scalable way.

AlphaFold breaks new ground in demonstrating the stunning potential for AI as a tool to aid fundamental scientific discovery. DeepMind looks forward to collaborating with others to unlock that potential.

Statements from independent scientists:

Professor Venki Ramakrishnan, Nobel Laureate and President of the Royal Society
"This computational work represents a stunning advance on the protein-folding problem, a 50-year old grand challenge in biology. It has occurred decades before many people in the field would have predicted. It will be exciting to see the many ways in which it will fundamentally change biological research."

Professor Dame Janet Thornton, Director Emeritus & Senior Scientist, EMBL-EBI
"What the DeepMind team has managed to achieve is fantastic and will change the future of structural biology and protein research. After decades of studying proteins, the molecules that provide the structure and functions of all living things, I awoke this morning feeling that progress has been made."

Arthur D. Levinson, PhD, Founder & CEO Calico, Former Chairman & CEO, Genentech
"AlphaFold is a once in a generation advance, predicting protein structures with incredible speed and precision. This leap forward demonstrates how computational methods are poised to transform research in biology and hold much promise for accelerating the drug discovery process."

Professor Andrei Lupas, Director, Max Planck Institute for Developmental Biology
"AlphaFold's astonishingly accurate models have allowed us to solve a protein structure we were stuck on for close to a decade, relaunching our effort to understand how signals are transmitted across cell membranes."

Professor Ewan Birney, Deputy Director General EMBL, Director EMBL-EBI
"I nearly fell off my chair when I saw these results. I know how rigorous CASP is - it basically ensures that computational modelling must perform on the challenging task of ab-initio protein folding. It was humbling to see that these models could do that so accurately. There will be many aspects to understand but this is a huge advance for science."

Statements from DeepMind / Alphabet:

Demis Hassabis, PhD, Founder and CEO, DeepMind
"The ultimate vision behind DeepMind has always been to build AI and then use it to help further our knowledge about the world around us by accelerating the pace of scientific discovery. For us AlphaFold represents a first proof point for that thesis. This advance is our first major breakthrough in a long-standing grand challenge in science, which we hope will have a big real-world impact on disease understanding and drug discovery."

Pushmeet Kohli, PhD, Head of AI for Science, DeepMind
"These incredible results are testament to DeepMind's unique research philosophy - bringing together mission-focused, multidisciplinary teams to target ambitious scientific goals. Critical assessments like CASP are important for driving research progress, and we look forward to building on this work, deepening our understanding of proteins and biological mechanisms, and opening up new avenues of exploration."

John Jumper, PhD, AlphaFold Lead, DeepMind
"Protein biology is fantastically complex and defies simple characterisation. Our team's work demonstrates that machine learning techniques are finally able to meet the complexity of describing these incredible protein machines, and we are truly excited to see what new breakthroughs in both human health and fundamental biology it will bring."

Kathryn Tunyasuvunakool, PhD, Science Engineer, DeepMind
"The ability to predict high accuracy protein structures with AI could change how we approach biology, with potential applications in drug design and bioremediation. Particularly for experimentally challenging proteins, good predictive techniques could make a huge difference."

Sundar Pichai, CEO, Google and Alphabet
"This is an incredible AI-powered breakthrough in protein folding, which will help us better understand one of life's most fundamental building blocks. This huge leap forward from DeepMind has immediate practical implications, enabling researchers to tackle new and difficult problems, from future pandemic response to environmental sustainability."

Researchers at the University of Basel have discovered a molecular mechanism that plays a central role in intact long-term memory. This mechanism is also involved in physiological memory loss in old age.

Many life forms, from worms to humans, have differentiated memory functions, such as short-term and long-term memory. Interestingly, at the cell and molecule level, many of these functions are nearly identical from life form to life form. Detecting the molecules involved in memory processes is of great importance to both basic and clinical research, since it can point the way to the development of drugs for memory disorders.

By studying roundworms (Caenorhabditis elegans), scientists at the Transfaculty Research Platform for Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now discovered a molecular mechanism of long-term memory that is also involved in memory loss in old age. They report on their findings in the journal Current Biology.

The team led by Dr Attila Stetak, Professor Andreas Papassotiropoulos and Professor Dominique de Quervain used sensory stimuli to first examine the learning and memory ability of genetically modified roundworms lacking a certain gene, mps-2. This gene contains the blueprint for part of a voltage-dependent ion channel in the nerve cell membrane and is suspected of playing a role in memory functions.

It was found that modified worms had equally good short-term memory as unmodified specimens. However, as the length of the experiment increased, the researchers found that the genetically modified worms were less able to retain what they learned. Without mps-2, they had a reduced long-term memory.

Age-related memory loss

In roundworms, as in humans, a loss of memory can be observed with increasing age. However, the molecular basis for this process is largely unclear. In further experiments, the researchers were able to prove that unmodified worms with the mps-2 gene exhibit a strong reduction of the MPS-2 protein, the product of the gene, in old age. This was related to reduced memory performance.

This lack of MPS-2 protein proved not to be a passive but an actively regulated process. The research team was able to identify another protein, NHR-66, as responsible for regulating this deficiency. NHR-66 actively curbs the reading of the mps-2 gene and thus production of the MPS-2 protein in old age. If in older worms MPS-2 protein level was artificially induced or their NHR-66 was turned off, they had a similarly good memory as younger worms. Both molecules, MPS-2 and NHR-66, therefore make for interesting targets for drugs that could mitigate age-related memory loss. In further studies, the researchers want to examine therapeutic options based on their discovery.

Decades after two large earthquakes rocked the Mojave Desert in California, the discovery of new post-earthquake displacement features has prompted KAUST researchers to update the existing model for this earthquake-prone region. Their findings support a thin "crème brûlée" model in which the strength lies in the upper crust, while the lower crust exhibits more ductility over time than previously thought.

To understand how the Earth's lithosphere, the crust and upper mantle behave in earthquake cycles (before, during and after earthquakes) over time, scientists must determine how strength is distributed in the rock layers of the lithosphere.

"By strength, we mean how much force rocks can withstand over time," says Shaozhuo Liu, a postdoc who worked on the project with KAUST's Sigurjón Jónsson, together with researchers from California. "We are interested in rheology--how the rocks behave and 'flow' when forces are applied to them."

The occurrence of earthquakes, the evolution of fault zones, and the resulting topography are dictated by how lithospheric rocks respond to forces.

"Given that the majority of lithospheric rocks are located several kilometers below the surface, we cannot directly observe how they respond," says Liu. "Building rheological models based on observations collected at the surface is the best alternative."

After the two Mojave earthquakes, earthquake-induced displacements on the surface were studied extensively. Previous models favored a strong crust (both the upper and lower crust) and a low-viscosity upper mantle. However, the newly determined post-earthquake displacements lasted longer than expected, suggesting that physical processes in the lower crust were more active than previously thought.

"Building on our work on these displacement features in 2015," says Liu, "our current study sought to clarify the dominant processes that would produce such features."

Their findings suggest that, after around two years of continued slip both on and below the original ruptures, the following decades saw earthquake-induced viscoelastic relaxation as the dominant physical process in the lower crust and upper mantle. The team showed that the viscosity of the lower crust is about five times lower than previously thought and only marginally higher than that of the upper mantle; that is, the lower crust appears to be weaker than anticipated, supporting a thin-skinned "crème brûlée" model for the region.

"Revisiting well-studied sites has the potential to provide new insights into lithospheric rheology," says Jónsson. "This knowledge will help with regional hazard assessments for earthquake-prone highly populated territories like California."

Over a period of 39 months, invasive keyhole wasps (Pachodynerus nasidens) at the Brisbane Airport were responsible for 93 instances of fully blocked replica pitot probes - vital instruments that measure airspeed -- according to a study published November 30 in the open-access journal PLOS ONE by Alan House of Eco Logical Australia and colleagues. As noted by the authors, the results underscore the importance of risk-mitigating strategies, such as covering pitot probes when aircraft arrive and setting up additional traps to intercept the wasps.

Interactions between aircraft and wildlife are frequent and can have serious financial and safety consequences. But the risk posed by wildlife when aircraft are on the ground is much less understood, and specific threats posed by insects have not been quantified before. In the new study, House and his colleagues investigated the possible role of keyhole wasps in obstructing pitot probes at Brisbane Airport. A total of 26 wasp-related issues were reported at the airport between November 2013 and April 2019, in conjunction with a series of serious safety incidents involving pitot probes. In its native range in South and Central America and the Caribbean, the wasp is known to construct nests using man-made cavities, such as window crevices, electrical sockets, and of course, keyholes.

The researchers used 3D-printing technology to construct a series of replica pitot probes, which they mounted at four locations at the airport. All nests in these probes were made by keyhole wasps, and peak nesting occurred in the summer months. Nesting success (i.e., the proportion of nests producing live adults) was optimal between 24 and 31°C, and probes with apertures of more than 3 mm in diameter were preferred. The majority of nests were constructed in one area of the airport. The proportion of grassed areas within 1000 m of probes was a significant predictor of nesting, and the nest volume in pitot probes may determine the sex of emerging wasps. According to the authors, P. nasidens poses a significant risk to aviation safety, and further work is warranted to develop strategies for controlling or eradicating persistent populations of this adaptable, inventive, and highly mobile species.

The authors add: "We hope this research will bring attention to a little known but serious issue for air travel in tropical and sub-tropical regions. Having found its way across the Pacific Ocean, there is no reason to doubt that it could spread to other parts of Australia. The consequences of not managing this clever but dangerous pest could be substantial."

The covid-19 virus, like all viruses relies on their host for reproduction

How SARS-CoV-2 captures stoichiometric amino and nucleic acids in a human lung cell has been discovered by using a computational model by scientists from the University of Warwick

By understanding host-based metabolic perturbations inhibiting SARS-CoV-2, a rapid, experimentally testable generation of drug predictions can be made

A computational model of a human lung cell has been used to understand how SARS-CoV-2 draws on human host cell metabolism to reproduce by researchers at the University of Warwick. This study helps understand how the virus uses the host to survive, and enable drug predictions for treating the virus to be made.

Viruses rely on their host to survive, a crucial step of lifecycle is the synthesis of the virus particles within the host cell, therefore understanding this process is key to finding ways to prevent the virus from surviving.

Using a computer model of a human lung cell metabolism, scientists from the School of Life Sciences at the University of Warwick have captured the stoichiometric amino and nucleic acid requirements of SARS-CoV-2, the virus that causes Covid-19. Publishing their results in the paper, 'Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network', in the journal Life Science Alliance.

Their model has identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction, highlighting reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. In fact, researchers found that only few of these metabolic perturbations are able to selectively inhibit virus reproduction.

Researchers have also noted that some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA-interference techniques.

Professor Orkun Soyer, from the School of Life Sciences at the University of Warwick comments:

"We have created a stoichiometric biomass function for the COVID-19-causing SARS-CoV-2 virus and incorporated this into a human lung cell genome scale metabolic model.

"We then predicted reaction perturbations that can inhibit SARS-CoV-2 reproduction in general or selectively, without inhibiting the host metabolic maintenance. The predicted reactions primarily fall onto glycolysis and oxidative phosphorylation pathways, and their connections to amino acid biosynthesis pathways."

Dr Hadrien Delattre, from the School of Life Sciences at the University of Warwick adds:

"Together, these results highlight the possibility of targeting host metabolism for inhibition of SARS-CoV-2 reproduction in human cells in general and in human lung cells specifically.

He added, "More research needs to be carried out to explore SARS-CoV-2 infected cells and their metabolism, however the model developed here by the researchers can be used as a starting point for testing out specific drug predictions".

Glass sponges - as the name suggests - have a glass-based skeleton composed of a network of glass needles, hooks, stars, and spheres. To achieve such a unique architecture they have to manipulate the shape of disordered glass to form highly regular and symmetrical elements. Thin crystalline fibers made of a protein, known as silicatein, are present in channels inside of these glass elements. It is known that silicatein crystals are responsible for glass synthesis in sponges and for shaping the glass skeleton. However, until now efforts to determine the 3D structure of this protein, describe how it assembles into crystals, and how those form the glass skeleton were unsuccessful. Mainly, because nobody was able to reproduce these crystals in the lab.

A team of researchers led by Dr. Igor Zlotnikov from the B CUBE -Center for Molecular Bioengineering at TU Dresden tried an unusual approach. Instead of producing silicatein in the lab and trying to obtain lab-grown crystals to study the structure, the researchers decided to take the glass needles from a sponge skeleton and analyze the tiny crystals that already exist inside.

The Zlotnikov group together with researchers from the Dresden Center for Nanoanalysis (DCN) at the Center for Advancing Electronics Dresden (cfaed) used high-resolution transmission electron microscopy (HRTEM) to take a closer look at silicatein crystals packed inside the glass needles. "We have observed an exceptionally ordered and at the same time complex structure. Analyzing the sample we have seen that it is a mixture of an organic and inorganic matter. Meaning that both proteins and glass form a hybrid superstructure that somehow shapes the skeleton of sponges," explains Dr. Zlotnikov.

A traditional way of obtaining a 3D structure of a protein is to expose its crystal to a beam of X-rays. Each protein crystal scatters the X-rays in a different way providing a unique snapshot of its internal arrangement. By rotating the crystal and collecting such snapshots from many angles, the researchers can use computational methods to determine the 3D protein structure. Such an approach is widely used and is the basis of modern structural biology. It works well for crystals of at least 10 microns in size. However, the Zlotnikov group wanted to analyze silicatein crystals which were about 10 times smaller. When exposed to X-rays they were almost immediately damaged, making it impossible to collect a complete data set of snapshots from multiple angles.

With support from the team at PSI's Swiss Light Source (SLS), the researchers used a new emerging method known as serial crystallography. "You combine diffraction images from many crystals," says Filip Leonarski, beamline scientists at PSI, who was involved in the study. "With the traditional method you shoot a movie. With the new method you get many snapshot which you combine afterwards to decipher the structure." Each snapshot is taken at a different part of the tiny crystal or even from a different crystal.

In total, the researchers collected more than 3500 individual X-ray diffraction snapshots from 90 glass needles at completely random orientations. Using state-of-the-art computational methods they were able to find order within the chaos and assemble the data to determine the first complete 3D structure of silicatein.

"Before this study, the structure of silicatein was hypothesized based on its similarity to other proteins," says Dr. Zlotnikov. Using the newly obtained 3D structure of silicatein, the researchers were able to understand its assembly and function inside the glass skeleton of the sponge. They built a computational model of the superstructure within the glass needle and explained the initial complex images of the protein-glass superstructures obtained with the HRTEM.

"We provided detailed information on the existence of a functional 3D protein-glass superstructure in a living organism. In fact, what we describe is the first known naturally occurring hybrid mineral-protein crystalline assembly," concludes Dr. Zlotnikov.

ITHACA, N.Y. - Prohibiting fishing in conservation reserves is a common strategy for protecting ocean ecosystems and enhancing fisheries management. However, such dedicated reserves are rare in freshwater ecosystems, where conservation efforts generally piggyback on the protection of terrestrial habitats and species.

Now, a collaboration between researchers from Cornell University and the University of Wisconsin-Madison has found that small, community-based reserves in Thailand's Salween River Basin are serving as critical refuges for fish diversity in a region whose subsistence fisheries have suffered from decades of overharvesting.

The team's paper, "A Network of Grassroots Reserves Protects Tropical River Fish Diversity," published Nov. 25 in Nature.

The lead author is Aaron Koning, a former postdoctoral fellow with the Cornell Atkinson Center for Sustainability who is currently a postdoctoral researcher at the University of Nevada, Reno. The project was overseen by Pete McIntyre, the Dwight Webster Sesquicentennial Faculty Fellow and associate professor of natural resources and environment at Cornell University.

Freshwater ecosystems across the world have experienced rapid species declines compared to ecosystems on land or in the ocean. One of the leading causes is overfishing, particularly in regions where fish are a vital source of human nutrition.

Koning launched his work in Thailand as a doctoral student with McIntyre at the University of Wisconsin-Madison, with the goal of testing whether the benefits documented from marine conservation reserves might also apply to freshwater systems. Both researchers came to Cornell in 2018 and continued to work on the project with their collaborators at UW-Madison.

They focused on the Mae Ngao River along Thailand's border with Myanmar, because Southeast Asia has an unusually long history of freshwater conservation reserves. In 2012, Koning began documenting more than 50 reserves spread over 1,000 square kilometers of the river valley. Each of these reserves had been created by a local community to support its own nearby fishing grounds.

"It was really striking to see this largely uncoordinated effort of grassroots actors who pursued this fascinating conservation strategy of their own volition, and they keep doing it because they can see the benefits in their catches," Koning said. "That really motivated me to ask the questions: Why does this work and could it work elsewhere?"

The researchers surveyed fish communities in 23 separate reserves that ranged in length from 300 meters to 2 kilometers. Compared to adjacent areas where fishing is unrestricted and intense, the grassroots reserves contained on average 27% more fish species and 124% higher fish density, with a more than twentyfold increase in overall biomass.

"Generally, we think of rivers as systems where things flow through and fish move around constantly, so what effect could a small reserve possibly have?" Koning said. "But just having a few hundred meters where people aren't fishing, while they're fishing like crazy everywhere else, can consistently produce these big changes."

One of the key characteristics for successful reserves was location. When reserves are placed within view of local villages, the community members can enforce conservation rules and deter poachers.

"Residents can literally see the large fish from their homes - it's pretty compelling," McIntyre said.

Fish longer than 20 centimeters (approximately 8 inches) were almost entirely restricted to the reserves, and larger reserves saw the biggest bump in fish diversity and size. Community members reported that having the reserves over time helped them to catch larger fish. This indicates the reserves not only protect biodiversity but can also bolster the food security of local populations, especially during the dry season when farmers have collected their crops and turn to subsistence fishing to supplement their families' diets.

"As if the local benefits were not amazing enough, we were fascinated to see a further benefit of having other reserves nearby. These fish populations appear to be linked, yielding synergistic gains when the ad hoc network of reserves allows exchange among protected areas," McIntyre said.

The team's findings aligned with the theoretical predictions made by marine conservation models, which led the researchers to suspect the grassroots reserves could be a successful strategy for other regions that have been overharvested, such as in the Mekong, Amazon and Congo rivers, where intensive fisheries feed millions of people.

"This is a great example of communities engaging in conservation on their own, and being successful," Koning said. "If we can take that reality, mix it with what we already know from marine systems, then maybe we can marry these things and design a system of small reserves that maximize conservation benefits while improving fishery benefits for communities, too."

Koning is now working with Zeb Hogan, an aquatic ecologist at the University of Nevada-Reno who hosts the National Geographic network program "Monster Fish," to study this conservation approach at larger scales in the Mekong River basin.

COLUMBUS, Ohio - More Americans than not believe that college athletes should be allowed to be paid more than what it costs them to go to school, a new national study of nearly 4,000 people suggests.

Findings from the National Sports and Society Survey (NSASS), led by researchers at The Ohio State University, suggest that 51 percent of adults agree that college athletes should have the ability to be paid above school costs, 41 percent disagree and 8 percent don't know.

An analysis of the survey results, published this week in the Sociology of Sport Journal, found a variety of factors were linked to how Americans thought about the issue.

"We found that it was largely a story of race, ethnicity, views about discrimination in society and traditionalism," said Chris Knoester, lead author of the study and associate professor of sociology at Ohio State.

"A lot of the same issues concerning race that we're dealing with in the larger society seem to have played a role in how people felt about college athletes' economic rights."

Knoester conducted the study with David Ridpath, associate professor of sports management at Ohio University.

The NSASS is sponsored by Ohio State's Sports and Society Initiative. The survey was completed by 3,993 adults who volunteered to participate through the American Population Panel, run by Ohio State's Center for Human Resource Research. Participants, who came from all 50 states, answered the survey online between the fall of 2018 and spring of 2019.

Because NSASS participants are disproportionately female, white and Midwestern, the researchers weighted the survey results to more accurately reflect the U.S. population. (The unweighted sample found 48 percent agreed college athletes should be allowed to be paid, with 44 percent disagreeing.)

Participants were asked to rate, on a scale from "strongly disagree" to "strongly agree," how much they agreed with the statement "College athletes should be allowed to be paid, as athletes, more than it costs to go to school."

"We wanted to make it clear that we were talking about compensation over and above a scholarship and what it costs to go to school," Knoester said.

"Also, we didn't want to get into details about how to organize compensation. We just wanted to know if people thought it should be possible for college students to be paid as athletes."

The survey also asked a variety of questions designed to uncover the factors associated with support for paying athletes.

Results showed that the odds for white adults to strongly agree that college athletes should receive compensation beyond their scholarships were 36 percent lower than the odds for non-white adults.

When these differences were broken down further, Black adults had odds of strongly agreeing that college athletes should be paid more than it costs them to go to school that were 2.5 times those of white adults.

Hispanics were also more likely than whites to support athlete pay.

But it wasn't just a person's race and ethnicity that was important, Knoester said.

Findings showed that people were more likely to support paying college athletes if they agreed that discrimination was the main reason that non-whites had worse jobs, income and housing than white people in America.

Knoester noted that African American males make up less than 5 percent of the undergraduate population in U.S. colleges and universities, but about 55 percent of the participants in NCAA Division I men's basketball and football.

"We think that people who agree that racial and ethnic discrimination is a problem in our country also see that African American athletes are the ones most affected by the lack of pay in the major college sports," he said.

The research also found that people who might be viewed as "traditionalists" were more likely to oppose athlete pay. This included older adults, those who lived in rural areas and self-identified conservatives.

"Traditionalists are people who generally approve of the status quo, or have a nostalgia for the past, and often don't want to change things," Knoester said.

Some people have worried that paying college athletes would turn off the people most necessary for the success of college athletics: the fans.

But this study found that people who rated themselves as the most passionate sports fans were also more likely than others to support athlete pay.

There haven't been a lot of other national surveys examining views about college athletes' economic rights, Knoester said. But the few that have been conducted, such as the 2019 Seton Hall Sports Poll, also have similar results to this study.

"I think there's no doubt that there is increasing public opinion support for allowing college athletes to be paid," he said.

"Importantly, this trend is occurring when the NCAA is under enormous pressure to allow for greater compensation for college athletes."

Scientists studying the complex relationship between aging and memory have found that in a controlled experiment, people can remember the details about past events with a surprising 94% accuracy, even accounting for age. These results, published in the journal Psychological Science, suggest that the stories we tell about past events are accurate, although details tend to fade with time.

"These results are surprising to many, given the general pessimism about memory accuracy among scientists and the prevalent idea that memory for one-time events is not to be trusted," said Nicholas Diamond, the study's lead researcher, a former graduate student at Baycrest's Rotman Research Institute (RRI), and currently a postdoctoral researcher at the University of Pennsylvania.

About 400 academics, including memory scientists, surveyed as part of this study estimated memory accuracy to be around 40% at best, expecting this score to be even lower for older participants or when greater amounts of time had elapsed since the events.

"This study shows us that memory accuracy is actually quite good under normal circumstances, and it remains stable as we age," said Brian Levine, a senior scientist at RRI and a professor of psychology and neurology at the University of Toronto and co-author on the study. "These results will be helpful for understanding memory in healthy aging."

For their study, the researchers created an immersive, scientifically controlled event for their participants: a 30-minute audio-guided tour of art and other items displayed at Baycrest. Two days later, participants were asked to tell the researcher everything they could remember about the tour. The responses were recorded and then verified against the facts.

The researchers also tested Baycrest employees on their recall of a standardized, scripted procedure that they had experienced one month to three years prior. This allowed the researchers to examine the effect of delay between the event and memory recall, while the standardized nature of the procedure made it possible to verify accuracy.

Using standardized, verifiable events to test memory is an innovative approach, the researchers said, as scientists typically use artificial laboratory stimuli, such as random word lists, rather than real-life experiences, or they test participants' memory for personal past experiences, which cannot be verified.

"This pessimism originates from earlier studies showing that memory can be manipulated using certain testing methods," said Levine. "While those studies were important in showing the ways in which memory can fail, we wanted to know what happens when people freely recall events without such manipulation. We found that they are overwhelmingly accurate."

The results showed that participants' accuracy was high in both cases, though, as expected, the number of details they remembered decreased with age and time. At best, they recalled about 25% of their experience. "This suggests that we forget the majority of details from everyday events, but the details we do recall correspond to the reality of the past," Diamond said.

In a related study also published in Psychological Science, Diamond and Levine examined the degree to which people's memories matched the true order of events. In this case, younger adults tended to perform better than older adults, suggesting that while accuracy of details remains high with age, older adults are less likely to correctly remember the true sequence of past events. That is, the order of our memories becomes disorganized as we age.

"The results of these studies can contribute to identifying differences in memory among those who develop dementia," said Dr. Levine.

CHAMPAIGN, Ill. -- The brains of healthy adults recovered faster from a mild vascular challenge and performed better on complex tests if the participants consumed cocoa flavanols beforehand, researchers report in the journal Scientific Reports. In the study, 14 of 18 participants saw these improvements after ingesting the flavanols.

Previous studies have shown that eating foods rich in flavanols can benefit vascular function, but this is the first to find a positive effect on brain vascular function and cognitive performance in young healthy adults, said Catarina Rendeiro, a researcher and lecturer in nutritional sciences at the University of Birmingham who led the research with University of Illinois at Urbana-Champaign psychology professors Monica Fabiani and Gabriele Gratton.

"Flavanols are small molecules found in many fruits and vegetables, and cocoa, too," Rendeiro said. "They give fruits and vegetables their bright colors, and they are known to benefit vascular function. We wanted to know whether flavanols also benefit the brain vasculature, and whether that could have a positive impact on cognitive function."

The team recruited adult nonsmokers with no known brain, heart, vascular or respiratory disease, reasoning that any effects seen in this population would provide robust evidence that dietary flavanols can improve brain function in healthy people.

The team tested the 18 participants before their intake of cocoa flavanols and in two separate trials, one in which the subjects received flavanol-rich cocoa and another during which they consumed processed cocoa with very low levels of flavanols. Neither the participants nor researchers knew which type of cocoa was consumed in each of the trials. This double-blind study design prevents researchers' or participants' expectations from affecting the results.

About two hours after consuming the cocoa, participants breathed air with 5% carbon dioxide - about 100 times the normal concentration in air. This is a standard method for challenging brain vasculature to determine how well it responds, Gratton said.

The body typically reacts by increasing blood flow to the brain, he said.

"This brings in more oxygen and also allows the brain to eliminate more carbon dioxide," he said.

With functional near-infrared spectroscopy, a technique that uses light to capture changes in blood flow to the brain, the team measured oxygenation in the frontal cortex, a brain region that plays a key role in planning, regulating behavior and decision-making.

"This allows you to measure how well the brain defends itself from the excess carbon dioxide," Fabiani said.

Researchers also challenged participants with complex tasks that required them to manage sometimes contradictory or competing demands.

Most of the participants had a stronger and faster brain oxygenation response after exposure to cocoa flavanols than they did at baseline or after consuming cocoa lacking flavanols, the researchers found.

"The levels of maximal oxygenation were more than three times higher in the high-flavanol cocoa versus the low-flavanol cocoa, and the oxygenation response was about one minute faster," Rendeiro said.

After ingesting the cocoa flavanols, participants also performed better on the most challenging cognitive tests, correctly solving problems 11% faster than they did at baseline or when they consumed cocoa with reduced flavanols. There was no measurable difference in performance on the easier tasks, however.

"This suggests that flavanols might only be beneficial during cognitive tasks that are more challenging," Rendeiro said.

Participants varied in their responses to cocoa flavanols, the researchers found.

"Although most people benefited from flavanol intake, there was a small group that did not," Rendeiro said. Four of the 18 study subjects had no meaningful differences in brain oxygenation response after consuming flavanols, nor did their performance on the tests improve.

"Because these four participants already had the highest oxygenation responses at baseline, this may indicate that those who are already quite fit have little room for improvement," Rendeiro said. "Overall, the findings suggest that the improvements in vascular activity after exposure to flavanols are connected to the improvement in cognitive function."

The images reveal that vibrational strong coupling can be achieved, which is a phenomenon that recently attracts wide attention for its potential use to control fundamental physical and chemical material properties. The result could lead the development of a novel platform for on-chip chemical identification of tiny amounts of molecules and for studying fundamental aspects of strong coupling phenomena on the nanometer scale. The work has been published in Nature Photonics (DOI: 10.1038/s41566-020-00725-3).

Light plays an essential role in modern science and technology, with applications ranging from fast optical communication to medical diagnosis and laser surgery. In many of these applications, the interaction of light with matter is of fundamental importance.

At infrared frequencies, light can interact with molecules via their vibrations that occur at molecule-specific frequencies. For that reason, molecular materials can be identified by measuring their infrared reflection or transmission spectra. This technique, often called infrared fingerprint spectroscopy, is widely used for the analysis of chemical, biological and medical substances.

Recently, it was found that the interaction between infrared light and molecular vibrations can be so strong that eventually the material properties are modified, such as conductivity and chemical reactivity. This effect - called vibrational strong coupling - can occur when a material is placed into a microcavity (typically formed by mirrors that are separated by micrometer-size distances) in which the light is concentrated.

The strength of the interaction between light and matter strongly depends on the amount of matter. Consequently, the interaction weakens when the number of molecules is reduced, challenging infrared spectroscopy applications and eventually preventing strong vibrational coupling to be achieved. This problem can be overcome by concentrating light in nanocavities or by compressing its wavelength, which leads to light confinement.

"A particularly strong compression of infrared light can be achieved by coupling it to lattice vibrations (phonons) of thin layers of high-quality polar crystals. This coupling leads to the formation of infrared waves - so-called phonon polaritons - that propagate along the crystal layer with a wavelength that can be more than ten times smaller than that of the corresponding light wave in free space", says Andrei Bylinkin, first author of the work.

Now, the researchers have studied the coupling between molecule vibrations and propagating phonon polaritons. First, they placed a thin layer of hexagonal boron nitride (less than 100 nm thick) on top of organic molecules. Hexagonal boron nitride is a van der Waals crystal from which thin high-quality layers can be easily obtained by exfoliation. Next, it was necessary to generate phonon polaritons in the thin boron nitride layer. "This cannot be achieved by just shining infrared light onto the boron nitride layer, because the momentum of light is much smaller than the momentum of the phonon polaritons", says Andrei Bylinkin.

The problem of the momentum mismatch was solved with the help of the sharp metal tip of a scanning near-field microscope, which acts as an antenna for infrared light and concentrates it to a nanoscale infrared spot at the tip apex that provides the necessary momentum to generate phonon polaritons. The microscope also plays a second important role. "It allowed us for imaging the phonon polaritons that propagate along the boron nitride while interacting with the nearby organic molecules", says Rainer Hillenbrand who led the study. "That way we could observe in real space how the phonon polaritons couple with the molecular vibrations, thereby forming hybrid polaritons", he added.

The set of images that were recorded at various infrared frequencies around the resonance of the molecular vibrations revealed various fundamental aspects. The hybrid polaritons are strongly attenuated at the frequency of the molecular vibration, which could be interesting for future on-chip sensing applications. The spectrally resolved images also showed that the waves propagate with negative group velocity, and most important, that the coupling between the phonon polaritons and the molecular vibrations is so strong that it falls into the regime of vibrational strong coupling.

"With the help of electromagnetic calculations we could confirm our experimental results, and further predict that strong coupling should be possible even between few atom thick layers of boron nitride and molecules", says Alexey Nikitin.

The possibility of strong vibrational coupling on the extreme nanometer scale could be used in the future for development of ultrasensitive spectroscopy devices or to study quantum aspects of strong vibrational coupling that have been not accessible so far.

Protocell compartments used as models for an important step in the early evolution of life on Earth can be made from short polymers. The short polymers, which better approximate the likely size of molecules available on the early Earth, form the compartments through liquid-liquid phase separation in the same manner as longer polymers. Although they have no membrane separating them from their environment, the protocells can sequester RNA and maintain distinct internal microenvironments, in some ways even outperforming similar compartments made from longer polymers.

A paper describing the research, by Penn State scientists, appears November 23, 2020 in the journal Nature Communications.

"An important step for the early evolution of life on Earth is compartmentalization," said Christine Keating, Distinguished Professor of Chemistry at Penn State and one of the leaders of the research team. "Living things need to be somehow separated from their environment. We wanted to know if we could make compartments that could function like protocells out of molecules that were more similar in size to the molecules that would have been available on Earth when life was beginning."

The researchers create the compartments, called 'complex coacervates,' by combining two oppositely charged polymers in a solution. The polymers are attracted to each other and can form droplets through liquid-liquid phase separation, similar to oil droplets forming in a salad dressing as it separates. Depending on the conditions, the polymers can remain uniformly distributed in the solution, they can form the protocell-like coacervates, or they can clump together to form solid aggregates.

The researchers compared different lengths of polymers composed of charged units, from 1 to 100 units. The longer polymers have higher charges, are more strongly attracted to each other, and can form compartments more easily in a broader set of experimental conditions.

"We tested a large number of combinations of polymers types and lengths to try to establish the parameters for compartment formation," Fatma Pir Cakmak, a graduate student at Penn State at the time of the research and first author of the paper. "We found that polymers as short as five units long could form stable compartments."

The researchers then tested the ability of the compartments made from the short polymers to perform certain functions of a protocell. The compartments were stable in a variety of salt concentrations and, depending on the polymer combinations, were able to maintain an apparent pH inside that compartment that was different than the pH of the surrounding solution.

"We don't know what the conditions were in which life formed," said Saehyun Choi, a graduate student at Penn State and one of the authors of the paper. "It could have been in the ocean, in brackish water, or in freshwater. The compartments were stable in salt concentrations high enough to suggest that they are a relevant model for any of these situations."

When single-stranded RNA molecules were added to the solution, compartments made from shorter polymers were better able to sequester the RNA than compartments made from longer polymers. RNA molecules inside the compartments were concentrated by as much as 500 times the surrounding solution. Double-stranded RNA molecules were also sequestered by the compartments and were more stable in the compartments made from shorter polymers.

The research team also tested the ability of RNA to maintain its folding and three-dimensional structure inside the compartments.

"Under the conditions that we tested, RNA formed much of its secondary structure but did not maintain its fully native folding inside the compartments," said McCauley O. Meyer, a graduate student at Penn State and an author of the paper. "We saw basically no difference based on the size of the polymers forming the compartments, so it may just be that we didn't have enough of a key component--something like magnesium, which is important for fully native RNA folding."

The results show that even with simple small components, compartments that are capable of many of the hallmarks of protocells can be made.

"It's a powerful finding to see that we can make these compartments out of such short polymers and in some ways, like accumulating RNAs, they function better than ones made from longer polymers," said Keating. "Our findings suggest that even if only smaller molecules were available on the early Earth, functional compartments could form. Over time, larger molecules could have been incorporated as they became available."

The researchers emphasize that the polymers they are using capture the essence of plausible early-Earth molecules but are likely not like the ones available on the early Earth, except in size. They stated that they are not attempting to recreate the conditions of early Earth that led to the evolution of life.

"What we're after is not the precise transcript of what happened on Earth billions of years ago," said Phil Bevilacqua, Distinguished Professor of Chemistry and of Biochemistry and Molecular Biology at Penn State and one of the leaders of the research team. "Instead, we want to know how feasible it is for life to start. We're exploring boundary conditions, and you have to have short polymers before you get long polymers."

Boston - Results of a new study show that opioid overdose deaths involving more than one substance (polysubstances) are more common than opioid-only overdose deaths among youth. Led by researchers at Boston Medical Center's Grayken Center for Addiction, the data shows that cocaine and other stimulants like crystal methamphetamine are the substances most commonly involved in opioid overdose deaths in young people between the ages of 13 and 25. The study also provides novel data about opioid overdose deaths involving stimulants in young people, as those rates increased 351 percent between 2010 and 2018. Published in JAMA Pediatrics, the study emphasizes that in order to address the national overdose crisis, special attention must be paid to adolescents and young adults, and cannot focus solely on opioids.

A study published in 2018 found that 8,986 adolescents and young adults died from opioid poisoning between 1999 and 2016, and the mortality rate increased 268 percent during that time. Data from the Centers for Disease Control and Prevention (CDC) shows an increase in opioid overdose deaths involving other substances in adults, including cocaine and methamphetamine, between 1999 and 2018.

"Our study provides significant insight into what is driving opioid-related overdoses among adolescents and young adults, which can help improve treatment and outcomes in this population," said Scott Hadland, MD, pediatrician and addiction specialist at Boston Medical Center who serves as the study's senior author. Hadland is also an assistant professor of pediatrics at Boston University School of Medicine.

Researchers utilized cross-sectional data from the CDC's Wide-Ranging Online Data for Epidemiologic Research. They included entries categorized as deaths involving multiple causes, and identified deaths involving opioids such as fentanyl, heroin, and prescription pills for the period between January 1999 and December 2018 in youth aged 13 to 25 years. Opioid overdose death data were captured and further broken down by the presence of other substances, including benzodiazepines, alcohol, antidepressants, cannabis, antipsychotics, barbiturates, cocaine and other psychostimulants. Data involving sex, age, race/ethnicity and census region were also analyzed.

The rates of opioid-only and polysubstance-involved opioid overdose deaths increased dramatically during the study period, by 384 and 760 percent, respectively. In 2018, there were 4,623 opioid overdose deaths among youth, and synthetic opioids were most commonly involved (73 percent). Of those deaths, more than half (2,476) involved multiple substances, meaning that overdoses deaths involving more than just opioids were more common than those involving opioids alone. Stimulants, mainly cocaine, contributed to 1,541 opioid overdose deaths, which represented more than 33 percent of total overdoses and 66 percent of the polysubstance overdose deaths in 2018.

"These results emphasize that we need to be focusing on more than just opioids when treating young people with opioid use disorder," said Jamie Lim, MD, a pediatrics resident at BMC and Boston Children's Hospital, who is the study's corresponding author. "As providers, we need to recognize that co-occurring substance use disorders are common, and they must be addressed simultaneously when treating opioid addiction."

American alligators are about as close to dinosaurs as you can get in modern times, and can grow up to 14 feet in length. While much smaller reptiles such as lizards are able to regenerate their tails, the question of whether the much larger alligator is able to regrow their massive tails has not been well studied. A team of researchers from Arizona State University and the Louisiana Department of Wildlife and Fisheries have uncovered that young alligators have the ability to regrow their tails up to three-quarters of a foot, or 18% of their total body length.

An interdisciplinary team of scientists used advanced imaging techniques combined with demonstrated methods of studying anatomy and tissue organization to examine the structure of these regrown tails. They found that these new tails were complex structures with a central skeleton composed of cartilage surrounded by connective tissue that was interlaced with blood vessels and nerves. They speculate that regrowing their tails gives the alligators a functional advantage in their murky aquatic habitats.

The findings are published in the journal Scientific Reports.

"What makes the alligator interesting, apart from its size, is that the regrown tail exhibits signs of both regeneration and wound healing within the same structure," said Cindy Xu, a recent PhD graduate from ASU's molecular and cellular biology program and lead author of the paper. " Regrowth of cartilage, blood vessels, nerves, and scales were consistent with previous studies of lizard tail regeneration from our lab and others. However, we were surprised to discover scar-like connective tissue in place of skeletal muscle in the regrown alligator tail. Future comparative studies will be important to understand why regenerative capacity is variable among different reptile and animal groups."

"The spectrum of regenerative ability across species is fascinating, clearly there is a high cost to producing new muscle," said Jeanne Wilson-Rawls, co-senior author and associate professor with ASU's School of Life Sciences. "

"Staff biologists in our Alligator Research and Management Program have been pleased to partner with Dr. Kusumi at Arizona State University for many years," said Ruth M. Elsey, a Biologist Manager with the Louisiana Department of Wildlife and Fisheries. "We see alligators in the field with some indication of possible regrowth of tail tissue, but their expertise led to the current study detailing the histological changes associated with the capacity for possible partial tail regrowth or wound repair."

Alligators, lizards, and humans all belong to a group of animals with backbones called amniotes. While the interdisciplinary team has previous studied the ability of lizards to regenerate their tails, this finding of regrowth of complex new tails in the alligator gives further information about the process in amniotes.

"The ancestors of alligators and dinosaurs and birds split off around 250 million years ago," said co-senior author Kenro Kusumi, professor and director of ASU's School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. "Our finding that alligators have retained the cellular machinery to regrow complex tails while birds have lost that ability raises the question of when during evolution this ability was lost. Are there fossils out there of dinosaurs, whose lineage led to modern birds, with regrown tails? We haven't found any evidence of that so far in the published literature."

"If we understand how different animals are able to repair and regenerate tissues, this knowledge can then be leveraged to develop medical therapies," said Rebecca Fisher, co-author and professor with the University of Arizona College of Medicine-Phoenix and ASU's School of Life Sciences. The researchers hope their findings will help lead to discoveries of new therapeutic approaches to repairing injuries and treating diseases such as arthritis.