Earth

Lysophospholipids are phospholipids that have just one fatty acid chain, and in recent years, the role of lysophospholipids in physiology and pathophysiology has attracted attention. Lysophosphatidylethanolamine (LPE) is a type of lysophospholipid that are reportedly present in the brain that consist of many species with different fatty acid chain lengths and degrees of unsaturation. The latest studies in animal models have reported elevated levels of LPE in the brain after traumatic brain injury and cerebral ischemia. Fluctuations in LPE concentration have also been reported in the plasma of patients with major depression and Alzheimer's disease. Although these reports suggest the involvement of LPE in brain function, the role of LPE in the brain has remained unclear.

Therefore, a team of doctors led by Shinshu University's Institute for Biomedical Sciences first analyzed the composition of LPE species in the mouse brain using mass spectrometry and decided to investigate the role of 18: 1 LPE in nerve cells, which is abundant in the brain. As a result, it was clarified that 18: 1 LPE has a function of promoting neurite outgrowth of cerebral cortical neurons. Furthermore, it was revealed that 18: 1 LPE protects neurons from cell death due to glutamate toxicity. These results suggested that LPE plays an important role in brain function. This is the first elucidation of the role of LPE in neurons of the central nervous system. Glutamate toxicity is considered to be a major cause of nerve cell death due to acute diseases such as brain damage and cerebral ischemia, and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Therefore, our finding is expected to contribute to the development of treatment for these nerve damage.

Corresponding author of the study Dr. Takeshi Uemura states, "the study confirmed that 18: 1 LPE, which is one of the LPE species most abundant in the brain, has a function of promoting neurite outgrowth and protecting against neuronal cell death due to glutamate toxicity. It is suggested that LPE plays an important role in brain function."

The research group would like to further elucidate the physiological importance of LPE in the brain. Since there are other LPE species that are abundant in the brain besides 18: 1 LPE, the research group will investigate how other LPE species work in the brain. They will work with animal models to confirm whether symptoms such as nerve damage are improved by administration of LPE.

From a molecular biology perspective, it is important to clarify the receptor of LPE. The group believe that identifying specific receptors for individual LPEs and clarifying their signal transduction pathways will be the key to elucidating the physiological and pathophysiological roles of LPEs in the brain. The research group at Shinshu University's Institute for Biomedical Sciences hopes to lead the development of neuroprotective and therapeutic agents for cranial nerve damage targeting LPE and its receptors.

LA JOLLA, CA--Scientists at Scripps Research have unveiled a new Ebola virus vaccine design, which they say has several advantages over standard vaccine approaches for Ebola and related viruses that continue to threaten global health.

In the new design, described in a paper in Nature Communications, copies of the Ebola virus outer spike protein, known as the glycoprotein, are tethered to the surface of a spherical carrier particle. The resulting structure resembles the spherical appearance of common RNA viruses that infect humans--and is starkly different from the snake-like shape of the Ebola virus.

The scientists say the design is intended to stimulate a better protective immune response than standard vaccine approaches, which often expose the immune system to individual glycoproteins rather than realistic-looking virus particles.

In designing the vaccine, the researchers also modified the outer spike protein to be more stable than the normal, "wild-type" version found in actual Ebola virus. In tests in mice and rabbits, they showed that this stabilized version elicited virus-neutralizing antibodies more strongly than the wild-type glycoprotein used in prior Ebola vaccine approaches.

"Here, we did a step-by-step investigation of glycoprotein stability and how that affects the vaccine's ability to elicit antibodies," says Jiang Zhu, PhD, associate professor in the Department of Integrative Structural and Computational Biology at Scripps Research and inventor of the vaccine. "In the end, we were able to develop a really promising vaccine design."

Continued viral threat

Ebola virus is endemic in various African bat species and can jump to humans, causing outbreaks of hemorrhagic fever with high mortality rates. The largest known outbreak of occurred in West Africa during 2013-2016, killing more than 11,000 people.

About two decades ago, Canadian researchers developed a vaccine against Zaire ebolavirus, more commonly known as Ebola virus. The vaccine, which was later licensed to a major pharma company and is called rVSV-ZEBOV, uses a live virus--vesicular stomatitis virus--which has been modified to include the gene for the Ebola virus glycoprotein.

When injected, the rVSV-ZEBOV vaccine infects cells and produces copies of the glycoprotein, eliciting an immune response to protect against future exposure to Ebola virus. Tests in Africa amid the aforementioned outbreak suggested it worked well and it was approved by the Food and Drug Administration in late 2019. However, those tests lacked placebo groups and other standard features of typical large-scale phase-III trials. Thus, questions remain on true efficacy.

In developing their new ebolavirus vaccine design, Zhu and his team focused on the relative instability of the glycoprotein structure as a potential factor in vaccine effectiveness. They investigated the molecular sources of this instability in detail, and eventually came up with a set of modifications that greatly stabilize the glycoprotein. In mice and rabbits, their modified glycoprotein elicited a more potent neutralizing antibody response against two different ebolaviruses--the Makona strain of Ebola virus and the Uganda strain of Bundibugyo ebolavirus--and compared those with the wild-type glycoprotein.

The team's design also included special protein segments that self-assemble tightly into a ball-shaped "nanoparticle" that support multiple glycoproteins on their surface. This nanoparticle-based structure presents the glycoproteins to the immune system similar to common human viruses, and thus the body has learned to recognize the spherical particles.

"Think of our nanoparticle as your sport vehicle, with a roof rack that carries a mountain bike and a trunk where you stow your clothes, gears and food," Zhu explains. "The only difference here is that the Ebola virus spike is your mountain bike, and the locking domains and T-cell epitopes are your stuff in the trunk. We call that a multilayered design."

A new approach

This nanoparticle design is distinctively different from other nanoparticle platforms. Zhu explains that in his team's design, the genetic codes of the optimized glycoprotein, the nanoparticle-forming unit, the locking domain and the T-cell epitope are all contained in a single piece of DNA. In cells, this DNA generates a single protein chain that can self-assemble, forming the right structure and associating with other identical chains to create a virus-like protein ball with multiple layers.

"The idea is that the all-in-one design simplifies the manufacturing process and drives the vaccine cost lower," Zhu says.

His team already has used the nanoparticle platform to create a COVID-19 vaccine candidate, which has shown in animal models that it can induce a powerful antibody response to both SARS-CoV-1 and SARS-CoV-2. It also has shown to be effective against variants.

For Ebola virus, the nanoparticle-based vaccines showed far better results in mouse and rabbit virus-neutralization tests that tests that used only glycoproteins to stimulate immune response. Inoculating animals with the Ebola wild-type glycoprotein, which tends to fall apart, led to signs suggesting a vaccine phenomenon known as antibody-dependent enhancement--in which a vaccine elicits not only virus-neutralizing antibodies, but also antibodies that paradoxically increase the virus's ability to infect cells. The researchers found that their best nanoparticle-based designs only minimally elicit these bad antibodies.

"There are a lot of things in the Ebola virus vaccine field that still need to be examined carefully, but in this study, we ended up with two nanoparticle-based designs that seem very suitable for further optimization and testing," Zhu says.

He says the vaccine approach can be extended to other members of the same virus family, such as Marburg virus, which is also a major threat. Ebolaviruses and marburgvirus both belong to a group of viruses, known as filoviruses, that have a bizarre thread-like shape when seen under a microscope.

The study also included atomic-level crystal structures on the modified glycoproteins, which was done in collaboration with the laboratory of Ian Wilson, DPhil, the Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology.

COLUMBUS, Ohio - Neighborhoods without opioid treatment providers likely serve as a widespread barrier to care for those who are ready to seek help, a new study has found.

The study, led by researchers at The Ohio State University, appears today (May 12, 2021) in the journal PLOS ONE.

"The study identified clear opioid treatment deserts that undoubtedly stand in the way of access to needed care and that likely exist throughout the state and the nation. These are areas where treatment providers should be setting up shop - we need a surge of resources into these areas," said Ayaz Hyder, an assistant professor in Ohio State's College of Public Health and leader of the study team.

The team used 2013-2017 data from emergency management services agencies throughout Franklin County - home to Ohio's capital, Columbus. In 2017, Ohio had the second-highest drug overdose mortality rate in the nation - 46.3 deaths per 100,000 people.

The researchers mapped 6,929 EMS runs during which medics administered the overdose drug naloxone to adult patients. They compared the locations of those runs to the distance and/or time to travel to the closest treatment provider that offered medication-assisted treatment services, including treatment with methadone or buprenorphine.

An area was defined as a desert if the distance to a provider was a mile or more away (about two minutes by car) or more than 30 minutes away on public transportation. Previous research has suggested that the likelihood of someone staying in treatment for a complete cycle drops by as much as 50% when the treatment provider is more than a mile away.

The median travel time by car in this study was two minutes. By public transit, it was 17 minutes. But the study found it was rather common for the distance to fall outside of the ideal proximity to longer-term treatment for opioid use disorder. The researchers also observed shorter travel times by public transit for white adults compared to Black adults.

"We found large swaths of the county where people experienced an overdose but had no nearby option for treatment," said Hyder, who is a core faculty member of Ohio State's Translational Data Analytics Institute.

Gretchen Hammond, a study co-author and a lecturer in Ohio State's College of Social Work, stressed the importance of recognizing and reacting to barriers based on distance to care.

"Proximity matters - it is arduous to have to travel far to receive vital services," Hammond said. "We often overlook travel time and distance. We think because something is on the bus line that it is accessible. Not if that bus ride is 1.5 hours one way."

Areas closer to major highways and main streets and the Columbus downtown area showed greater accessibility. But the research showed that treatment deserts were common elsewhere in the county.

The researchers wanted to understand not only how far treatment might be by car, but by public transportation - a mode used by many who are in recovery and a potential obstacle particularly outside of the city center.

Even those with access to a car, or who know a family member or someone else who could drive them, may favor public transportation for appointments, Hyder said.

"Even if you are in a high resource neighborhood there is still stigma attached to seeking treatment. If you want to seek treatment on your own, without telling friends or family, you might still be living in a treatment desert where nothing is accessible to you by public transit.

"Access to treatment needs to be equitable and we need to eliminate the accessibility problem," Hyder said, adding that an increasing percentage of drug overdose deaths are among Black Americans.

"Some of the treatment deserts that we're identifying are also in places where racism and discrimination are at play in terms of the resources available. That's another significant obstacle to access," he said.

Since the initial study, Hyder and colleagues have been expanding on the model they used for the research and want to one day be able to offer treatment providers throughout Ohio and beyond a snapshot of where they should open new centers.

Already, the research team has been able to advise treatment providers on locations within Franklin County where no recovery services have been available so that they can pursue options where there are pockets of need for accessible treatment services. The team is currently working in partnership with public health, health care and community organizations to translate overdose data to action by decision-makers as part of a strategy to address the opioid epidemic.

"We've been able to say, here's a ZIP code where you can really make an impact," Hyder said, adding that he'd like to develop a public-facing map that allows both providers and addiction and mental health boards the opportunity to plan in ways likely to reach more people with opiate misuse disorders.

Elephant Seals' Extreme Diving Allows Them to Exploit Deep Ocean Niche

Using data captured by video cameras and smart accelerometers attached to female elephant seals, Taiki Adachi and colleagues show that the animals spend at least 80% of their day foraging for fish, feeding between 1,000 and 2,000 times per day. The unique glimpse at elephant seal foraging strategy shows how these large marine mammals exploit a unique ocean niche filled with small fish. The findings also may offer a way to monitor the health of the mesopelagic zone, the dark and cold ocean "twilight zone" ecosystem at 200 to 1,000 meters deep. Small mesopelagic fish dominate the world's ocean biomass, but little is known about the mesopelagic zone or how it is affected by global climate change. Large marine mammals can dive deep to find food in this zone, but the bigger they are, the more food they need to sustain themselves. Massive marine mammals like sperm whale solve this problem by diving into the mesopelagic zone to eat large prey like jumbo squid. The data collected by Adachi et al. suggest that the smaller elephant seals solve the problem by eating abundant small mesopelagic fish, but the smaller mouthfuls mean they must dive repeatedly to maintain a positive energy balance. The researchers say that elephant seal foraging activity could be used to trace the future health of mesopelagic fish populations, as the mesopelagic zone is expected to undergo substantial changes in temperature and oxygenation by the end of the century.

What The Study Did: Rates of preterm birth and stillbirth in Ontario, Canada, during the first six months of the COVID-19 pandemic are evaluated in this study.

Authors: Andrea N. Simpson, M.D., M.Sc., of St Michael's Hospital, Unity Health Toronto, in Toronto, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10104)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Scientists have developed a brain-computer interface (BCI) designed to restore the ability to communicate in people with spinal cord injuries and neurological disorders such as amyotrophic lateral sclerosis (ALS). This system has the potential to work more quickly than previous BCIs, and it does so by tapping into one of the oldest means of communications we have--handwriting.

The study, published in Nature, was funded by the National Institutes of Health's Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative as well as the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Deafness and Other Communication Disorders (NIDCD), both part of the NIH.

Researchers focused on the part of the brain that is responsible for fine movement and recorded the signals generated when the participant attempted to write individual letters by hand. In doing so, the participant, who is paralyzed from the neck down following a spinal cord injury, trained a machine learning computer algorithm to identify neural patterns representing individual letters. While demonstrated as a proof of concept in one patient so far, this system appears to be more accurate and more efficient than existing communication BCIs and could help people with paralysis rapidly type without needing to use their hands.

"This study represents an important milestone in the development of BCIs and machine learning technologies that are unraveling how the human brain controls processes as complex as communication," said John Ngai, Ph.D., director of the NIH BRAIN Initiative. "This knowledge is providing a critical foundation for improving the lives of others with neurological injuries and disorders."

When a person becomes paralyzed due to spinal cord injury, the part of the brain that controls movement still works. This means that, while the participant could not move his hand or arm to write, his brain still produced similar signals related to the intended movement. Similar BCI systems have been developed to restore motor function through devices like robotic arms.

"Just think about how much of your day is spent on a computer or communicating with another person," said study co-author Krishna Shenoy, Ph.D., a Howard Hughes Medical Institute (HHMI) Investigator and the Hong Seh and Vivian W. M. Lim Professor at Stanford University. "Restoring the ability of people who have lost their independence to interact with computers and others is extremely important, and that is what is bringing projects like this one front and center."

First, the participant was asked to copy letters that were displayed on the screen, which included the 26 lower-case letters along with some punctuation: ">" which was used as a space and "~" which was used as a "full stop." At the same time, implanted electrodes recorded the brain activity from approximately 200 individual neurons that responded differently while he mentally "wrote" each individual character. After a series of training sessions, the BCI's computer algorithms learned how to recognize neural patterns corresponding to individual letters, allowing the participant to "write" new sentences that hadn't been printed out before, with the computer displaying the letters in real time.

"This method is a marked improvement over existing communication BCIs that rely on using the brain to move a cursor to "type" words on a screen," said Frank Willett, Ph.D., an HHMI Research Scientist at Stanford University and the study's lead author. "Attempting to write each letter produces a unique pattern of activity in the brain, making it easier for the computer to identify what is being written with much greater accuracy and speed."

Using this system, the participant was able to compose sentences and communicate with others at a speed of about 90 characters per minute, comparable to someone of a similar age typing on a smartphone. In contrast, "point-and-click" interfaces have only achieved about 40 characters per minute.

This system also provides a level of flexibility that is crucial to restoring communication. Some studies have gone as far as attempting direct thought-to-speech BCIs that, while promising, are currently limited by what is possible through recordings from the surface of the brain which averages responses across thousands of neurons.

"Right now, other investigators can achieve about a 50-word dictionary using machine learning methods when decoding speech," said Dr. Shenoy. "By using handwriting to record from hundreds of individual neurons, we can write any letter and thus any word which provides a truly 'open vocabulary' that can be used in most any life situation."

For individuals who are paralyzed or living with "locked-in syndrome" due to brainstem stroke or late-stage ALS, the ability to communicate is largely or even completely lost without technological intervention. While preliminary, the technologies being developed here offer the potential to help those who have completely lost the ability to write and speak.

"Communication is central to how we function in society," said Debara L, Tucci, M.D., M.S., M.B.A, director, NIDCD. "In today's world of internet-based communication, people with severe speech and physical impairments can face significant communication barriers and, potentially, isolation. We hope these findings will encourage commercial development of this latest BCI technology."

In the future, Dr. Shenoy's team intends to test the system on a patient who has lost the ability to speak, such as someone with advanced ALS. In addition, they are looking to increase the number of characters available to the participants (such as capital letters and numbers).

The clinical trial, called BrainGate2, a collaboration of internationally recognized laboratories, universities, and hospitals working to advance brain-computer interface technologies, is testing the safety of BCIs that directly connect a person's brain to a computer. The study was a collaboration between Dr. Shenoy's and Jaimie Henderson, M.D.'s research group at Stanford University, Leigh Hochberg, M.D., Ph.D. from Brown University, Massachusetts General Hospital, and Providence VA and sponsor-investigator of the BrainGate2 trial. Dr. Henderson at Stanford University also performed the surgery to place the necessary electrodes.

"Thanks to the pioneering spirit of the participants in BrainGate, we are able to gain new insights into human brain function, which could lead to the creation of systems that will help others with paralysis," said Dr. Hochberg.

Researchers from the £12 million Developing Human Connectome Project have used the dramatic advances in medical imaging the project has provided to visualise and study white matter pathways, the wiring that connects developing brain networks, in the human brain as it develops in the womb.

Published today in Proceedings of the National Academy of Sciences of The United States of America, the study used magnetic resonance images (MRI) with unprecedented resolution from more than 120 healthy fetuses across the second and third trimesters of pregnancy to define how the structural connections in their brains first develop.

This is the largest and most detailed publicly available fetal MRI data set which will be released through the developing Human Connectome Project with other state-of-the-art fetal MR data including anatomical and functional images.

The diffusion data acquired were significantly richer than any previous data in this population, giving researchers much more sensitivity and specificity with respect to the location, shape and structure of the white matter tracts.

Sian Wilson, MRC-Sackler PhD student in the School of Biomedical Engineering & Imaging Sciences at King's College London said the work is significant as it is increasingly recognised that many injuries that take place during the fetal period often affect white matter development.

From a clinical point of view, the results help to understand what the normal trajectories of white matter look like so they can be used as a reference for when problems arise.

Crucially, before these advanced MR methods were possible, this kind of insight could only be achieved through studying small numbers of post-mortem samples and very little was known about how maturation occurs in the healthy fetal brain.

The results demonstrate that different white matter tracts in the brain mature at different rates and have distinct development trajectories. This implies important differences in the timing of vulnerability for different white matter tracts. Understanding this vulnerability has implications for the best time to try and treat diseases affecting the developing white matter such as those affecting preterm infants.

"Similar studies in the past included fetuses with brain injuries in their datasets, meaning characterisation of normal development was not possible" Ms Wilson said.

"In this cohort, our population did not have any abnormalities so it gives unique insight into how normal development takes place and over a timeframe in development when the most dramatic changes in the white matter structure are taking place."

Dr Tomoki Arichi, MRC Clinician Scientist and Clinical Senior Lecturer in the Department of Perinatal Imaging & Health at the School of Biomedical Engineering & Imaging Sciences at King's College London, said the study and the fetal cohort is a huge advance in what is known about white matter development in the human brain.

"The study is the culmination of 5 years' work on the dHCP to build towards a point where we can get really robust diffusion MRI data from this incredibly challenging population, and so represents a landmark for providing in-vivo visualisation of how white matter first develops in the human brain," he said.

"The applications of the findings are exciting because we can now compare these normal developmental trajectories to those from other large existing cohorts with abnormalities such as babies born preterm"

Intelligent materials, the latest revolution in the field of materials science, can adapt their properties depending on changes in their surroundings. They can be used in everything from self-healing mobile phone screens, to shape-shifting aeroplane wings, and targeted drug delivery. Delivering drugs to a specific target inside the body using intelligent materials is particularly important for diseases like cancer, as the smart material only releases the drug payload when it detects the presence of a cancer cell, leaving the healthy cells unharmed.

Now, researchers from the Centre for Advanced 2D Materials (CA2DM) at the National University of Singapore (NUS) have created a new class of intelligent materials. It has the structure of a two-dimensional (2D) material, but behaves like an electrolyte - and could be a new way to deliver drugs within the body.

Just like traditional electrolytes, these new "2D-electrolytes" dissociate their atoms in different solvents, and become electrically charged. Furthermore, the arrangement of these materials can be controlled by external factors, such as pH and temperature, which is ideal for targeted drug delivery. The 2D-electrolytes also show promise for other applications that require a material to be responsive to environmental changes, such as artificial muscles and energy storage.

The team behind the 2D-electrolytes is led by Professor Antonio Castro Neto, Director of CA2DM, and comprised researchers from CA2DM, as well as the NUS Department of Physics, and the NUS Department of Materials Science and Engineering.

Their trailblazing results were published in the prestigious journal Advanced Materials on 12 May 2021.

Changing the behaviour of 2D materials

In materials science, a 2D material is a solid material that exists in a single layer of atoms. It can be thought of as an atomically-thin sheet that has a specific height and width, but effectively no depth, hence, it is essentially two-dimensional. On the other hand, an electrolyte is a substance that produces an electrically conducting suspension when dissolved in a solvent, such as water.

There are numerous 2D materials in existence today, and electrolytic behaviour has been well-established in countless other compounds. However, the results from the NUS researchers show the first instance of materials that have both 2D structure and properties of electrolytes, with a particular trend to shape shift their form reversibly in liquid medium. The NUS team achieved this feat by using organic molecules as reactive species to add different functionalities to 2D materials such as graphene and molybdenum disulfide (MoS2).

"By adding different chemical groups that become positively or negatively electrically charged in solvents, we altered traditional 2D materials and came up with a novel class of smart materials that have their electronic properties controlled by morphological conformation," explained Prof Castro Neto.

The methods used by the researchers to create 2D-electrolytes are only a few possible examples among many potential options, making this discovery an exciting new research area to explore.

From a flat sheet to a rolled-up scroll

A major breakthrough of this research was that the orientation of the 2D-electrolytes could reversibly change by tweaking the external conditions. Currently, the electrical repulsion between the surface charge in a 2D material leads to it be laid out in a flat sheet. By altering the pH, the temperature, or the ionic concentration of the suspensions, the NUS researchers demonstrated the ability of the 2D-electrolyte sheet to shape shift and form scroll-like arrangements. These experimental results are supported by detailed theoretical analysis in which they explain the physical mechanism behind the scroll formation and stability.

These scroll orientations have such a small diameter that they could be described as one-dimensional (1D), leading to different physical and chemical properties. Moreover, this transition from 2D to 1D is reversible by altering the external conditions back to their original values

"One can think of 2D-electrolytes as the higher dimensional analogues of 1D electrolytes, commonly known as polyelectrolytes," said Prof Castro Neto. Important examples of polyelectrolytes include many biologically relevant materials, such as DNA and RNA.

"When acids, bases, or salts are added, these electrically charged polymers also undergo conformational transitions from molecular chains that are 1D to globular objects of 0D, and vice versa. Our 2D-electrolytes, in analogy with polyelectrolytes, show reversible transitions from 2D to 1D, as a function of external factors. As stimuli responsive materials, they are suitable for the creation of cutting-edge technology," he added.

Next steps

Discovering this class of materials has opened up new areas of exploration for materials scientists, since it brings together two fields of research that have been traditionally unlinked, namely, 2D materials in the field of Physics, and electrolytes (in the area of Electrochemistry).

"There is an uncountable number of ways to functionalise graphene and other 2D materials to transform them into 2D-electrolytes. We hope that our work will inspire scientists from different fields to further explore the properties and possible applications of 2D-electrolytes. We anticipate that as 2D-electrolytes have similarities with biological or natural systems, they are capable of spontaneously self-assemble and cross-link to form nanofibers that are promising for applications in filtration membranes, drug delivery, and smart e-textiles," explained Prof Castro Neto.

An enzyme could make a dream come true for the energy industry: It can efficiently produce hydrogen using electricity and can also generate electricity from hydrogen. The enzyme is protected by embedding it in a polymer. An international research team with significant participation of scientists from Technical University of Munich (TUM) has presented the system in the renowned science journal Nature Catalysis.

Fuel cells turn hydrogen into electricity, while electrolysers use electricity to split water to produce hydrogen. Both need the rare and thus expensive precious metal platinum as a catalyst. Nature has created a different solution: Enzymes, referred to as hydrogenases. They catalyze the conversion of hydrogen very quickly and almost without energy loss.

However, in the past these biocatalysts were not considered suitable for industrial use because of their high sensitivity to oxygen. Now a research team from the Technical University of Munich (TUM), Ruhr-Universität Bochum (RUB), the French National Centre for Scientific Research (CNRS) in Marseille and the Max-Planck Institute for Chemical Energy Conversion has succeeded in embedding the sensitive enzymes in a protective polymer in a way that makes them viable for use in technical hydrogen conversion.

Durability vs. activity

"When the sensitive hydrogenases are embedded in suitable polymers they continue to work for several weeks, even in the presence of oxygen," says Nicolas Plumeré, Professor for Electrobiotechnology at the TUM Campus Straubing for Biotechnology and Sustainability. "Without this protection they lose their activity within a matter of minutes."

Embedding the hydrogenases in polymers whose side chains can transfer electrons, referred to as redox polymers, had nevertheless two decisive disadvantages: a high level of resistance countervailed the flow of electrons through the redox polymer. This required the investment of energy which was then lost in the form of heat. And the embedded hydrogenases completely lost their ability to generate hydrogen.

Fine tuning potential

With a clever selection of the right polymer side chains, the research team has now succeeded in setting the redox potential of the polymer in such a way that only a small overvoltage is necessary to overcome the resistance.

More detailed investigations then revealed that the potential of the side chains had shifted slightly to positive values due to the embedding in the polymer matrix. In a further attempt they used a side chain with a corresponding negative potential. This trick was the breakthrough: The hydrogenase was now capable of catalyzing the reaction in both directions without energy loss.

Biocatalyst for hydrogen conversion

Utilizing this system the research team then built a fuel cell, in which oxygen is reduced by the enzyme bilirubin oxidase from the bacterium Myrothecium verrucaria, while the hydrogenase embedded in the polymer film oxidizes the hydrogen from the bacterium desulfovibrio desulfuricans, generating electricity in the process.

The cell achieved a value, with an open circuit voltage of 1.16 V, the highest ever measured for a system of this type and close to the thermodynamic maximum. With three milliamperes per square centimeter the cell achieved a very high power density for biological cells at the same time.

The system can also be used for the reverse reaction, producing hydrogen by consuming electrons: The energy conversion efficiency is close to 100 percent, even with power densities of over four milliamperes per square centimeter.

Blueprint for new biocatalysts

"The reduction in energy loss has two decisive advantages," says Nicolas Plumeré. "First, it makes the system significantly more efficient; second, the heat generated in a fuel cell stack at high performance levels would pose a problem for biological systems."

In order to make their system competitive with systems that use platinum-based catalysts, the team's ongoing research is now focused on improving the stability of the hydrogenases at higher power densities.

Furthermore, the findings can also be transferred to other highly-active but sensitive catalysts for energy conversion and electrosynthesis. Direct objectives here are primarily carbon dioxide-reducing enzymes that can use electricity to produce liquid fuels or intermediate products from carbon dioxide.

Acta Pharmaceutica Sinica B Volume 11, Issue 4 Publishes

https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b/vol/11/issue/4

Special Issue: The Biological Fate of Drug Nanocarriers

This special issue includes seven review and nine research articles from some leading scientists in the field that further the discussion on subtopics of in vivo fate of drug nanocarriers.

Guest Editors: Wei Wu, Professor, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China; Tonglei Li, Professor, Department of Industrial & Physical Pharmacy, Purdue University, West Lafayette, IN, USA; Ying Zheng, Professor, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association, Acta Pharmaceutica Sinica B (APSB) is a monthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences -- including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

Featured papers in this issue are:

Intracellular uptake of nanocrystals: Probing with aggregation-induced emission of fluorescence and kinetic modelling by authors Jifen Zhang, Clairissa D. Corpstein and Tonglei Li, (https://doi.org/10.1016/j.apsb.2020.09.017). Nanocrystals of tetrakis (4-hydroxyphenyl) ethylene (THPE) were incubated with KB cells and the intracellular uptake was characterized by confocal microscopy and flow cytometry based on aggregation-induced emission property of THPE, as well as quantitative analyses of THPE. The intracellular dissolution kinetics model was established to further understand the cellular absorption mechanism of nanocrystals.

Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study by authors Wenhao Wang, Zhengwei Huang, Yanbei Li, Wenhua Wang, Jiayu Shi, Fangqin Fu, Ying Huang, Xin Pan and Chuanbin Wu (https://doi.org/10.1016/j.apsb.2020.10.023). Different protein corona formation phenomena were shown in solid lipid nanoparticles (SLNS) with the various size and medium pH. The biological effect and the underlying interaction mechanisms were studied to provide a systematic perspective.

In vivo dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging by authors Yinqian Yang, Yongjiu Lv, Chengying Shen, Tingting Shi, Haisheng He, Jianping Qi, Xiaochun Dong, Weili Zhao, Yi Lu, and Wei Wu (https://doi.org/10.1016/j.apsb.2020.08.002 Authentic in vitro?in vivo correlation should be established between in vitro dissolution and in vivo dissolution which however has never been determined accurately. This study provides proof of concept of in vivo dissolution based on live imaging of fluorescently hybridized crystals of a model poorly water-soluble drug fenofibrate.

Other articles published in the issue include:

Reviews

Innate and adaptive immune responses toward nanomedicines

Iara Maíra de Oliveira Vian, Sabrina Roussel, Joan Defrên, Eliana Martins Lim, Frédéric Barabé, Nicolas Bertrand

https://doi.org/10.1016/j.apsb.2021.02.022

Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles

Anan Yaghmur, Huiling Mu

https://doi.org/10.1016/j.apsb.2021.02.013

Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

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Woods Hole, Mass. (May 12, 2021) -- Low-to-mid latitude land surfaces at low elevation cooled on average by 5.8 ± 0.6 degrees C during the Last Glacial Maximum (LGM), based on an analysis of noble gases dissolved in groundwater, according to a new study published in Nature.

Temperature estimates in the study are substantially lower than indicated by some notable marine and low-elevation terrestrial studies that have relied on various proxies to reconstruct past temperatures during the LGM, a period about 20,000 years ago that represents the most recent extended period of globally stable climate that was substantially cooler than present.

"The real significance of our paper is that prior work has badly underestimated the cooling in the last glacial period, which has low-balled estimates of the Earth's climate sensitivity to greenhouse gases," said paper co-author Jeffrey Severinghaus, a professor of geosciences at Scripps Institution of Oceanography, University of California San Diego. "The main reason that prior work was flawed was that it relied heavily on species abundances in the past. But just like humans, species tend to migrate to where the climate suits them. Think, for instance, of snowbirds moving from Canada to Arizona in winter. So, species aren't very good thermometers."

The paper does broadly support a recent marine proxy study by Tierney et al. published last year that found substantially greater low-latitude cooling than previous efforts and, in turn, suggested greater climate sensitivity than prior studies. That earlier paper suggested the equilibrium response of Earth's global-mean surface temperature is 3.4 degrees C per doubling of atmospheric carbon dioxide, in line with the consensus range of estimates from state-of-the-art climate models, but somewhat higher than the usual best estimate of 3.0 degrees C.

"The rather high climate sensitivity that our results suggest is not good news regarding future global warming, which may be stronger than expected using previous best estimates. In particular, our global review reinforces the finding of several single noble gas case studies that the tropics were substantially cooler during the last glacial maximum than at present. The unpleasant implication for the future is that the warmest regions of the world are not immune to further heating," commented co-author Werner Aeschbach, a professor at the Institute of Environmental Physics, Heidelberg University, Heidelberg, Germany.

The paper made use of a technique in which measurements of noble gases dissolved in ancient groundwater enable direct and quantitative determination of past surface temperature. Noble gases in the atmosphere are chemically and biologically inactive and have no appreciable sinks or sources over the 40,000-year timescales relevant to this study. They dissolve into groundwater, and their equilibrium concentrations depend strongly on temperature. The authors compiled four decades worth of groundwater noble gas data from every continent except Antarctica, along with previously unpublished measurements from some key tropical locations to produce a global record of noble gas-derived temperatures (NGTs) of the LGM.

"Noble gas paleo temperature records are so powerful because they are based on a physical principle and are not much influenced by life--which always complicates everything-- and short term extreme events." said journal article co-author Martin Stute, a professor in the Environmental Science Department at Barnard College and an adjunct senior research scientist at the Lamont-Doherty Earth Observatory. "They provide a temperature average over hundreds to thousands of years. It is remarkable, and rewarding for me, how consistent noble gas paleo temperature reconstructions are in low latitudes from the early studies that I led in the 1990s to the most recent ones."

The study bolsters the method of analyzing noble gases to reconstruct paleo temperatures and provides more confidence in climate models, according to the authors.

"Another key goal of our study was to evaluate the overall accuracy of the so-called 'noble gas paleo-thermometer' for reconstructing temperatures on land during the last glacial period. Naturally, our ability to confidently use this tool to understand the past is related to how well it works in the present. By comparing modern temperature observations to independent estimates using noble gases in relatively young groundwater, we found that the noble gas thermometer is remarkably accurate over a wide temperature range from around 2 to 33 degrees C (36 to 91 degrees F). This adds a good deal of confidence to our estimates of cooling during the LGM," said the paper's lead author, Alan Seltzer, an assistant scientist in the Marine Chemistry and Geochemistry Department at the Woods Hole Oceanographic Institution.

Seltzer added that the new analysis is important because climate models "provide an important tool that policy makers can use to decide on how to prepare for future environmental changes. This study alleviates the concern that, based on LGM proxy data, models might over-predict the global mean temperature response to carbon dioxide. In fact, based on both our study and the recent marine-proxy compilation, it is becoming clear that paleoclimate proxies and models are in agreement."

University of Cincinnati researchers studied the teeth of prehistoric horses and bison in the Arctic to learn more about their diets compared to modern species.

What they found suggests the Arctic 40,000 years ago maintained a broader diversity of plants that, in turn, supported both more -- and more diverse -- big animals.

The Arctic today is spartan compared to the wildlife-rich landscape during the ice ages of the Pleistocene epoch between 12,000 and 2.6 million years ago when wild horses, mammoths, bison and other big animals roamed the steppes and grasslands of what is now northern Canada, northern Europe, Alaska and Siberia. Short-faced bears, ground sloths and even cave lions called the 49th State home.

The Arctic supported greater populations as well, even compared to today's spectacular herds of caribou that can number more than 750,000 animals. The area supported between six and 10 times as many large animals as today's Arctic.

"In the Pleistocene, the diversity of wildlife was so much greater than we see today," UC assistant professor Joshua Miller said. "It looked completely different. A key question is why the the Arctic so depauperate by comparison today?"

The study was published in the journal Palaeogeography, Palaeoclimatology, Palaeoecology.

Researchers studied two of the most common big animals living between 12,000 and 40,000 years ago in what is now Alaska: horses and steppe bison, both of which went extinct due to climate change, human hunting or a combination of both.

UC doctoral student and lead author Abigail Kelly made dental casts of fossil specimens obtained from the University of Alaska Museum and subjected the fossil teeth to dental-wear analysis to evaluate the diet of these extinct animals.

"Because foods have different textures and interact with the enamel surface in different ways, we can look at different diets," Kelly said.

Teeth of plant-eating animals show different signs of wear depending on the type of food they chew. Grass is particularly abrasive because it contains silica that can wear down teeth over time. To the naked eye, grass-eating animals have teeth with blunter wear profiles (called mesowear). When viewed with a microscope, the teeth show parallel scratches. Animals that eat less grass and more leaves from trees, herbs and shrubs have relatively sharper teeth with fewer microscopic scratches.

UC researchers found the wear patterns on the teeth of steppe bison had fewer scratches than modern plains bison that eat mostly grass but more scratches than European bison, which likely feed on more woody plants. Similarly, prehistoric horses had teeth that bore different wear patterns compared to modern horses, suggesting their diet contained fewer abrasive grasses. Prehistoric bison and horses probably ate a more varied diet rich in broadleaf herbaceous plants than today's bison and horses.But the researchers said the microwear patterns could be a reflection of the seasonal foods the animal ate in the months before it died.?

The study suggested the Arctic had a broader mix of vegetation than exists today.

"It seems like the diets of bison and horses were not that different. They were eating similarly textured foods," Miller said. "But their physiology is quite different. Bison are foregut fermenters that digest food differently compared to hindgut fermenters such as horses. So there is potential for species to get different levels of nutrition from the same food."

The study has pressing relevance for conservation of wood bison, which were hunted to extinction in the United States in the 1900s. Populations from Canada were reintroduced to Alaska in 2015. North America's largest land animal, the wood bison, is a descendant of plains bison that migrated northward about 10,000 years ago and briefly coexisted with the steppe bison before replacing them.

Biologist and study co-author Tom Seaton is overseeing the reintroduction of wood bison for the Alaska Department of Fish and Game. He said their analysis offers important perspectives on how diverse populations of herbivores coexisted on the Alaska landscape thousands of years ago that could help biologists understand the needs of wood bison today.

Steppe bison survived thousands of years longer than horses, even though both relied on similar foods, according to UC's tooth analysis.

But it's likely the bison and horses evolved to use the landscape's resources in different ways -- a phenomenon called "niche partitioning." Horses and bison also have important differences in the way they digest food.

"This study provides insights for Alaska's wood bison restoration project through perspectives of niche partitioning between large herbivores on Alaska's modern landscape," Seaton said. "My hope is that this study will provide one more piece in the puzzle of bison restoration in the north."

While grazers like horses and bison went extinct in the Arctic, browsers such as moose and caribou that subsist mostly on leaves and woody plants still persist.

"What's interesting is why it's the grazers that go extinct while the browsers make it through," Miller said.

Miller has led numerous research expeditions deep into the Arctic National Wildlife Refuge by rigid inflatable boat to collect caribou antlers to track their historic migrations.

"The impacts of climate on vegetation can create a sudden shift," he said. "The cooler, drier environments of the late Pleistocene allowed megafauna to thrive. But the warm and wet climates of the Holocene led to today's wet tundra vegetation."

For her next project, doctoral student Kelly will take a closer look at bison and horses in the Yukon that lived around the same time.

"We'll be focusing on the story of how bison responded to the environmental changes of the last 50,000 years, as northern climates swung from relatively mild conditions, to extremely cold and dry during the last Glacial period, and finally rapid warming to the boreal forest climate we see today," she said. "Are bison able to change their diets in response to changing vegetation, or are they fixed within one niche?"

BOSTON - (May 12, 2021) - Scientists are rapidly gathering evidence that variants of gut microbiomes, the collections of bacteria and other microbes in our digestive systems, may play harmful roles in diabetes and other diseases. Now Joslin Diabetes Center scientists have found dramatic differences between gut microbiomes from ancient North American peoples and modern microbiomes, offering new evidence on how these microbes may evolve with different diets.

The scientists analyzed microbial DNA found in indigenous human paleofeces (desiccated excrement) from unusually dry caves in Utah and northern Mexico with extremely high levels of genomic sequencing, says Joslin Assistant Investigator Aleksandar Kostic, PhD, senior author of a Nature paper presenting the work.

Performing genomic analysis more broadly and deeply than previous studies on ancient human gut microbiomes, the study was the first to reveal novel species of microbes in the specimens, says Kostic, who is also an Assistant Professor of Microbiology at Harvard Medical School.

In previous studies of children in Finland and Russia, Kostic and his colleagues showed that children in industrialized regions, who were much more likely to develop type 1 diabetes than those in non-industrialized areas, also had very different gut microbiomes. "We were able to identify specific microbes and microbial products that we believe hampered a proper immune education in early life," Kostic says. "And this leads later on to higher incidents of not just type 1 diabetes, but other autoimmune and allergic diseases."

So what would a healthy human microbiome look like before the effects of industrialization? "I'm convinced that you can't answer that question with any modern living people," says Kostic, who points that even tribes in extremely remote regions of the Amazon are contracting Covid-19.

Steven LeBlanc, an archeologist formerly with Harvard's Peabody Museum of Archaeology and Ethnology, came to Kostic with a dramatic alternative source: microbial DNA found in human paleofeces samples that museums have collected from arid environments in the North American Southwest.

Kostic and graduate student Marsha Wibowo took on the challenge, eventually comparing the DNA from eight exceptionally well-preserved ancient gut samples from dry caves (some dated as early as the first century of the current era) with DNA in 789 modern samples. Slightly more than half of the modern samples were from people on industrialized "Western" diets and the remainder from people consuming non-industrialized foods (grown mostly within their own communities).

The differences between microbiome populations were striking. For instance, a bacteria known as Treponema succinifaciens "is not in a single Western microbiome that we analyzed, but it's in every single one of the eight ancient microbiomes," Kostic says. The ancient microbiomes did match up more closely with modern non-industry microbiomes.

Strikingly, Wibowo found that almost 40% of the ancient microbial species had never been seen before. What might explain this high genetic variability?

"In ancient cultures, the foods you're eating are very diverse and can support a more eclectic collection of microbes," Kostic speculates. "But as you move toward industrialization and more of a grocery-store diet, you lose a lot of nutrients that help to support a more diverse microbiome."

The ancient microbiomes also had relatively higher numbers than the modern industrial microbiomes of transposases (transposable elements of DNA sequences that can change location in the genome).

"We think this could be a strategy for the microbes to adapt in an environment that shifts a lot more than the modern industrialized microbiome, where we eat the same things and live the same life more or less year-round," Kostic says. "Whereas in a more traditional environment, things change and microbes need to adapt. They might use this much larger collection of transposases to grab and collect genes that will help them adapt to the different environments."

Moreover, the ancient microbial populations incorporated fewer genes related to antibiotic resistance. The ancient samples also featured lower numbers of genes that produce proteins that degrade the intestinal mucus layer, which then can produce inflammation that is linked with various diseases.

Additionally, the work may shed light on a scientific controversy about whether populations of gut microbes are transmitted vertically from generation to generation of humans, or evolve primarily from surrounding environments.

Looking at the lineage of the common bacteria Methanobrevibacter smithii in the ancient samples, they found its evolution was consistent with a shared ancestral strain that has been dated to roughly when humans first migrated across the Bering Strait into North America. "These microbes, just like our own genomes, have been traveling with us," Kostic says.

The research project began with the need to identify uncontaminated human paleofeces samples that were preserved in unusually good condition. "When we reconstructed these genomes, we tried to be very conservative," Wibowo says.

In addition to carbon-14 dating, the scientists used dietary analyses and other methods to validate that the selected samples were indeed human and not contaminated by soil or by other animals such as dogs, she says. The investigators also confirmed that the chosen samples displayed the patterns of decay that all DNA is known to exhibit over time.

The team performed far deeper sequencing of DNA than what was achieved in previous efforts, at least 100 million reads, with 400 million reads of DNA for one specimen.

One collaborator, anthropologist Meradeth Snow, PhD, of the University of Montana at Missoula, led an initiative to get perspectives on the work from Native American Indigenous communities in the Southwest region. "We acknowledge and appreciate those individuals whose genetics and microbes were analyzed for this research, as well as present-day individuals with associated genetic or cultural heritage," the study emphasizes.

The researchers plan to expand their studies to many other ancient microbiome specimens, aiming to detect novel microbial species and trying to predict their metabolic functions. Kostic is intrigued by the possibility of resurrecting these ancient microbes in the lab, by inserting ancient genomes in the closest living bacterial species. "If we can grow them in the lab, we can understand the physiology of these microbes much, much better," he says.

LeBlanc helped the Joslin investigators gathered collaborators, eventually recruited from a dozen institutions. Among key contributions, Montana's Dr. Snow led the extraction and preparation of the ancient DNA, and Harvard's Christina Warinner, PhD, offered her expertise on the ancient human microbiome. "It's been amazing to learn from all of these brilliant collaborators," Wibowo says. "It really takes a village."

The ability to connect and feel a sense of belonging are basic human needs but new Swansea University research has examined how these are determined by more than just our personal relationships.

Research led by psychologist Professor Andrew Kemp, of the College of Human and Health Sciences, highlights the importance of taking a wider approach to wellbeing and how it can be influenced by issues such as inequality and anthropogenic climate change.

Professor Kemp worked with PhD student Jess Mead and consultant clinical psychologist Dr Zoe Fisher, of the University's Health and Wellbeing Academy, on the study which presents a transdisciplinary framework to help understand and improve wellbeing.

Professor Kemp said: "We define wellbeing as positive psychological experience, promoted by connections to self, community and environment, supported by healthy vagal function, all of which are impacted by socio-contextual factors that lie beyond the control of the individual."

The researchers say their latest findings, which have just been published in Frontiers in Psychology, are particularly topical as society looks to recover and learn from Covid-19.

He said: "Our framework has already contributed to a better understanding of how to protect wellbeing during the pandemic and has led to the development of an innovative wellbeing science intervention, targeting university students and people living with acquired brain injury."

Professor Kemp added: "We feel our invited paper is timely as it not only aligns with a post-pandemic future that requires societal transformation, but it also picks up on global efforts to promote planetary wellbeing.

"Globalisation, urbanisation and technological advancements have meant that humans have become increasingly disconnected from nature. This continues despite research showing that contact with nature improves wellbeing."

The research reveals the advantages to health and wellbeing derived from connecting to oneself, others and nature and emphasises a need for focused efforts to tackle major societal issues that affect our capacity for connection.

He added: "The poorest are disproportionally impacted by major societal challenges including increasing burden of chronic disease, societal loneliness and anthropogenic climate change.

"Economic inequality has adverse impacts on the entire population, not just the poor, so improving economic inequality is fundamental to improving population wellbeing."

Citrus greening disease was first discovered in Florida in 2005. Since then, production of oranges in the United States for processing has declined by 72 percent between the 2007-2008 growing season and the 2017-2018 growing season, primarily in Florida. The disease was discovered in California in 2012, and now the state is beginning to see a rapid increase of citrus greening disease.

As there is currently no cure for citrus greening disease, many growers are concerned about its rapid spread and many plant pathologists are focused on learning more about the complicated nature of this disease. To add to this growing body of knowledge about citrus greening disease, a group of scientists working in California, New York, and Washington compared the early responses of two citrus varieties, Lisbon lemon and Washington navel orange trees, to infection by Liberibacter asiaticus, the pathogen that causes citrus greening disease.

These scientists conducted a comprehensive molecular analysis that showed that Lisbon lemon trees had less of a molecular response to the pathogen than Washington navel orange trees. In part, this might be because leaves of infected lemons tended to accumulate micronutrients, which led to less of an impact on photosynthesis. Additionally, protease inhibitors, important for plant defense, were upregulated in lemons.

"These results may be important for developing varieties of citrus that are more tolerant or perhaps resistant to the HLB pathogen," said Carolyn Slupsky, a UC Davis-based systems biologist involved with the research. "Our research highlights some key features that differentiate more tolerant from more susceptible varieties of citrus and may be used to develop new cultivars that are resistant to the effects of this pathogen."

This study is the first to analyze the impact of the citrus greening disease pathogen on citrus metabolism prior to symptom development. "Understanding early response is important," added Slupsky. "As it may also help in developing technologies to detect the disease earlier."