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The genome in mitochondria -- the cell's energy-producing organelles -- is involved in disease and key biological functions, and the ability to precisely alter this DNA would allow scientists to learn more about the effects of these genes and mutations. But the precision editing technologies that have revolutionized DNA editing in the cell nucleus have been unable to reach the mitochondrial genome.
 

Now, a team at the Broad Institute of MIT and Harvard and the University of Washington School of Medicine has broken this barrier with a new type of molecular editor that can make precise C* G-to-T* A nucleotide changes in mitochondrial DNA. The editor, engineered from a bacterial toxin, enables modeling of disease-associated mitochondrial DNA mutations, opening the door to a better understanding of genetic changes associated with cancer, aging, and more.
 

The work is described in Nature, with co-first authors Beverly Mok, a graduate student from the Broad Institute and Harvard University, and Marcos de Moraes, a postdoctoral fellow at the University of Washington (UW).
 

The work was jointly supervised by Joseph Mougous, UW professor of microbiology and an investigator at the Howard Hughes Medical Institute (HHMI), and David Liu, the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad Institute, professor of chemistry and chemical biology at Harvard University, and HHMI investigator.
 

"The team has developed a new way of manipulating DNA and used it to precisely edit the human mitochondrial genome for the first time, to our knowledge -- providing a solution to a long-standing challenge in molecular biology," said Liu. "The work is a testament to collaboration in basic and applied research, and may have further applications beyond mitochondrial biology."
 

Agent of bacterial warfare
 

Most current approaches to studying specific variations in mitochondrial DNA involve using patient-derived cells, or a small number of animal models, in which mutations have occurred by chance. "But these methods pose major limitations, and creating new, defined models has been impossible," said co-author Vamsi Mootha, institute member and co-director of the Metabolism Program at Broad. Mootha is also an HHMI investigator and professor of medicine at Massachusetts General Hospital.
 

While CRISPR-based technologies can rapidly and precisely edit DNA in the cell nucleus, greatly facilitating model creation for many diseases, these tools haven't been able to edit mitochondrial DNA because they rely on a guide RNA to target a location in the genome. The mitochondrial membrane allows proteins to enter the organelle, but is not known to have accessible pathways for transporting RNA.
 

One piece of a potential solution arose when the Mougous lab identified a toxic protein made by the pathogen Burkholderia cenocepacia. This protein can kill other bacteria by directly changing cytosine (C) to uracil (U) in double-stranded DNA.
 

"What is special about this protein, and what suggested to us that it might have unique editing applications, is its ability to target double-stranded DNA. All previously described deaminases that target DNA work only on the single-stranded form, which limits how they can be used as genome editors," said Mougous. His team determined the structure and biochemical characteristics of the toxin, called DddA.
 

"We realized that the properties of this 'bacterial warfare agent' could allow it to be paired with a non-CRISPR-based DNA-targeting system, raising the possibility of making base editors that do not rely on CRISPR or on guide RNAs," explained Liu. "It could enable us to finally perform precision genome editing in one of the last corners of biology that has remained untouchable by such technology -- mitochondrial DNA."
 

"Taming the beast"
 

The team's first major challenge was to eliminate the toxicity of the bacterial agent -- what Liu described to Mougous as "taming the beast" -- so that it could edit DNA without damaging the cell. The researchers divided the protein into two inactive halves that could edit DNA only when they combined.
 

The researchers tethered the two halves of the tamed bacterial toxin to TALE DNA-binding proteins, which can locate and bind a target DNA sequence in both the nucleus and mitochondria without the use of a guide RNA. When these pieces bind DNA next to each other, the complex reassembles into its active form, and converts C to U at that location -- ultimately resulting in a C* G-to-T* A base edit. The researchers called their tool a DddA-derived cytosine base editor (DdCBE).
 

The team tested DdCBE on five genes in the mitochondrial genome in human cells and found that DdCBE installed precise base edits in up to 50 percent of the mitochondrial DNA. They focused on the gene ND4, which encodes a subunit of the mitochondrial enzyme complex I, for further characterization. Mootha's lab analyzed the mitochondrial physiology and chemistry of the edited cells and showed that the changes affected mitochondria as intended.
 

"This is the first time in my career that we've been able to engineer a precise edit in mitochondrial DNA," said Mootha. "It's a quantum leap forward -- if we can make targeted mutations, we can develop models to study disease-associated variants, determine what role they actually play in disease, and screen the effects of drugs on the pathways involved."
 

Future developments
 

One goal for the field now will be to develop editors that can precisely make other types of genetic changes in mitochondrial DNA.
 

"A mitochondrial genome editor has the long-term potential to be developed into a therapeutic to treat mitochondrial-derived diseases, and it has more immediate value as a tool that scientists can use to better model mitochondrial diseases and explore fundamental questions pertaining to mitochondrial biology and genetics," Mougous said.
 

The team added that some features of DdCBE, such as its lack of RNA, may also be attractive for other gene-editing applications beyond the mitochondria.
 

A rat is less likely to help a trapped companion if it is with other rats that aren't helping, according to new research from the University of Chicago that showed the social psychological theory of the "bystander effect" in humans is present in these long-tailed rodents.

The study, titled "The Bystander Effect in Rats," also demonstrated that in the presence of other potential helper rats, rats are more, rather than less, likely to help. Whether helping is facilitated or suppressed depends on the circumstances rather than on personal temperament or morals, a finding with implications for human society. The research, published in the July 8 issue of Science Advances, builds off previous research on rat empathy.

In 2011, Peggy Mason, PhD, professor of neurobiology and senior author of the study, and her UChicago team of researchers found that rats consistently freed trapped companions, even saving a bit of chocolate for them, and this behavior was driven by a rat version of empathy. A subsequent study showed that rats treated with anti-anxiety medication are less likely to free a trapped peer because they do not feel its anxiety. In another study, researchers found that rats only freed trapped rat strains that they had previous social experience with.

The roots of the classic bystander effect date back to 1964, when Catherine "Kitty" Genovese was murdered in a crowded residential neighborhood in Queens, New York. An account published in the New York Times reported that 38 bystanders saw the murder but did not intervene. Though this story was later proven inaccurate, it inspired psychologists Bibb Latané and John Darley to investigate why so many people would fail to help.

The pair tested human subjects alone and in the presence of "confederate" bystanders -- people who were part of the research team and were instructed not to help -- as they confronted a variety of experimental scenarios with someone (an actor) in distress. Latané and Darley consistently observed that subjects were far less likely to help in the presence of non-helping confederates than they were when tested alone. This phenomenon, referred to as the bystander effect, is now a pillar in psychology, included in every introductory textbook and class. The mechanism for the classic bystander effect is thought to be a diffusion of responsibility whereby people reason that they need not act because others in a group will.

First author John Havlik was a UChicago undergraduate in Mason's laboratory, when the topic of the bystander effect came up during a lab meeting.

"My students had been bugging me to do this experiment for years," said Mason. "But it wasn't until John came along and would not let the idea go that we took the plunge."

Havlik, now a student at the Yale School of Medicine, spearheaded experiments to examine whether rats, which lack complex reasoning skills, would show a classical bystander effect.

The research team used their trapped rat paradigm in combination with rats that were made into "confederates" by administering an antianxiety drug that made them indifferent to another rat's distress, ensuring that they would not help. The team found that rats tested with confederates were less likely to help than those tested alone -- a bystander effect in rats. Digging deeper, they saw that the presence of confederates blocked reinforcement for helping.

"It's worse to have a non-responsive audience than to be alone," Mason said. "The rats try helping, but it's just not a rewarding experience because the other rats don't appear to care. It's as though the rat was saying to himself, 'I helped yesterday and no one cared. Not doing that again.' "

Mason and her team then wanted to know how the presence of untreated rats affected the helping behavior. Counter to the prediction of the bystander effect, duos and trios of rats actually were more likely to help than solo rats.

"At first, I thought the experiment had failed," Havlik said. "But after doing more research into human studies, we realized that behavior has actually been mirrored in people, too."

In research published last year, an analysis of surveillance videos revealed that groups of bystanders helped in more than 90% of violent encounters.

"The reason we see these patterns of helpfulness goes deeper than the lessons we learned in kindergarten about being nice to each other," said study co-author Maura Jacobi, MD, a 2020 graduate of the University of Chicago Pritzker School of Medicine and co-first author of the study. "This is a phenomenon that's not exclusive to humans."

CAMBRIDGE, MA - Microparticles offer a promising way to deliver multiple doses of a drug or vaccine at once, because they can be designed to release their payload at specific intervals. However, the particles, which are about the size of a grain of sand, can be difficult to inject because they can get clogged in a typical syringe.

MIT researchers have now developed a computational model that can help them improve the injectability of such microparticles and prevent clogging. The model analyzes a variety of factors, including the size and shape of the particles, to determine an optimal design for injectability.

Using this model, the researchers were able to achieve a sixfold increase in the percentage of microparticles they could successfully inject. They now hope to use the model to develop and test microparticles that could be used to deliver cancer immunotherapy drugs, among other potential applications.

"This is a framework that can help us with some of the technologies that we've developed in the lab and that we're trying to get into the clinic," says Ana Jaklenec, a research scientist at MIT's Koch Institute for Integrative Cancer Research.

Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior authors of the study, which appears today in Science Advances. The paper's lead author is MIT graduate student Morteza Sarmadi.

Microparticle model

Microparticles range in size from 1 to 1,000 microns (millionths of a meter). Many researchers are working on using microparticles made of polymers and other materials to deliver drugs, and about a dozen such drug formulations have been approved by the FDA. However, others have failed because of the difficulty of injecting them.

"The major issue is clogging, somewhere in the system, that doesn't allow for the full dose to be delivered," Jaklenec says. "Many of these drugs don't make it past development because of the challenges with injectability."

Such drugs are usually injected intravenously or under the skin. Making sure that these drugs successfully reach their destinations is a key step in the drug development process, but it's one that is often done last, and can thwart an otherwise promising treatment, Sarmadi says.

"Injectability is a major factor in how successful a drug will be, but little attention has been paid to trying to improve administration techniques," he says. "We hope that our work can improve the clinical translation of novel and advanced controlled-release drug formulations."

Langer and Jaklenec have been working on developing hollow microparticles that can be filled with multiple doses of a drug or vaccine. These particles can be designed to release their payloads at different times, which could eliminate the need for multiple injections.

To improve the injectability of these and other microparticles, the researchers experimentally analyzed the effects of altering the size and shape of the microparticles, the viscosity of solution in which they are suspended, and the size and shape of the syringe and needle used to deliver them. They tested cubes, spheres, and cylindrical particles of different sizes, and measured the injectability of each one.

The researchers then used this data to train a type of computational model known as a neural network to predict how each of these parameters affect injectability. The most important factors turned out to be particle size, particle concentration in the solution, viscosity of the solution, and needle size. Researchers working on drug-delivering microparticles can simply input these parameters into the model and get a prediction of how injectable their particles will be, saving the time they would have had to spend building different versions of the particles and testing them experimentally.

"Instead of going through the experiments, and going back and forth, having no idea of how successful the system will be, you can use this neural network and it can guide you, early on, to have an understanding of the system," Sarmadi says.

Injectability boost

The researchers also used their model to explore how changing the shape of the syringe could affect injectability. They came up with an optimal shape that resembles a nozzle, with a wide diameter that tapers toward the tip. Using this syringe design, the researchers tested the injectability of the microparticles they described in a 2017 Science study, and found that they boosted the percentage of particles delivered from 15 percent to almost 90 percent.

"This is another way to maximize the forces that are acting on the particles and pushing the particles toward the needle," Sarmadi says. "It's a promising result that shows that there's huge room for improvement in the injectability of microparticle systems."

The researchers are now working on designing optimized systems for delivering cancer immunotherapy drugs, which can help stimulate an immune response that destroys tumor cells. They believe these types of microparticles could also be used to deliver a variety of vaccines or drugs, including small-molecule drugs and biologics, which include large molecules such as proteins.

Chinese researchers recently discovered a protein quality control mechanism called "reubiquitination". The mechanism, according to the researchers, could promote the elimination of misfolded membrane proteins, minimize their dwell time in cells, and thereby reduce their probability to form toxic aggregates in human body.

Discovered by a research team from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences, the "reubiquitinase" RNF126 adds a small protein called ubiquitin to the unfolded membrane protein intermediates in the cytosol, and targets them to the degradation machinery, proteasome, for destruction.

Misfolded proteins in cells and organisms should be cleared by a protein quality control mechanism called ubiquitin-proteasome system. If not, they tend to form pathological aggregates that are believed to damage cells (e.g., neurons), and ultimately cause various diseases of aging, such as neurodegeneration.

The results show that RNF126-mediated reubiquitination is important for normal cell physiology. Without reubiquitination, targeting of misfolded proteins to the proteasome could be delayed, and this increase the risk of protein aggregation and cellular stress, which could gradually lead to various diseases.

In addition, the function of RNF126 as a reubiquitinase might be required for rapid proliferation of certain cancer cells, making it a potential therapeutic target.

This work has been published online in July 8, 2020 in Molecular Cell, and it was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, and the Shanghai Municipal Science and Technology Major Project.

Army researchers developed a new way to protect and safeguard quantum information, moving quantum networks a step closer to reality.

Quantum information science is a rapidly growing interdisciplinary field exploring new ways of storing, manipulating and communicating information. Researchers want to create powerful computational capabilities using new hardware that operates on quantum physics principles.

For the Army, the new quantum paradigms could potentially lead to transformational capabilities in fast, efficient and secure collecting, exchanging and processing vast amounts of information on dynamic battlefields of the future.

Drs. Dan Jones, Brian Kirby and Michael Brodsky from the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, joined by Gabriele Riccardi and Professor Cristian Antonelli from the University of L'Aquila, studied sources of noise in quantum communication channels.

Noise is a common plague of any communication - anyone who has ever used a radio, a walkie-talkie or a phone experienced noisy reception now and then, Brodsky said. Communication engineers devise intricate schemes to remove the noise and to clean the transmitted signal as much as possible.

According to Brodsky, quantum communications are no different in their susceptibility to noise in communication channels. In fact, even more so than the regular classic communications because the quantum signals are extremely low power.

"To engineer a useful quantum network, we need to understand how far, how fast and how reliably we could send quantum information," Brodsky said. "That requires understanding of the noise in communication channels."

As the team modeled, emulated, characterized and measured different types of noise in quantum channels, the researchers realized that while some quantum noise types are impossible to filter out, others could be removed quite easily.

Surprisingly, it turns out that the bad noise could be converted into good noise by simply adding a cheap extra component to the quantum channel. Having this extra control allows them to tweak the channel and to adjust the properties of the noise that masks the transmitted signal.

The overall focus of the lab's Quantum Networking Group is to experimentally explore the most efficient and secure ways to create, store and process quantum information based on state-of-the-art photonic technologies of the day. The main workhorse of the group is the lab's quantum networking testbed that they have built at its headquarters in Adelphi, Maryland. Researchers use the quantum testbed to test-drive various photonic technological approaches to the fast and robust delivery of quantum information over large distances.

"We approach our research quite uniquely by wearing system engineer hats," Jones said.

The research scope of the group spans developing the architecture and operational principles of quantum networks, as well as understanding and mapping technological limitations to its practical implementation, and, finally, inventing methods and techniques to engineer around these limitations. The current research results belong to the latter two categories.

The next projects in the pipeline focus on demonstrating an intriguing way of completely error-free transmission of quantum information. Further down the line is creating a multi-user quantum network testbed deployed in the field and demonstrating secure secret sharing protocols between two distance metropolitan campuses.

The field of quantum information science is booming worldwide as it potentially leads to unsurpassed capabilities in computation, communication and networking. It offers new paradigms in the ways information is being handled, which would lead to secure secret sharing, distributed network sensing and efficient decision making.

"Our research results are a step towards arming the warfighter of the future with quantum advantages and a good example of how operationalizing science results in transformational overmatch," Brodsky said.

The group summarized their research results are in a paper, Exploring classical correlation in noise to recover quantum information using local filtering, accepted by the peer-reviewed New Journal of Physics.

Researchers from the School of Biological Sciences and Swire Institute of Marine Science at the University of Hong Kong are working to understand how the coral symbiosis may respond to global warming through changes in their microbiome, specifically their symbiotic algae. Using a newly developed method they revealed , which may be a determining factor in the sucthe metabolic function of algae changes in response to competition with other speciescess or failure of certain host-symbiont combinations.

The research, published in The ISME Journal, used single-celled algae (dinoflagellates) which were isolated from reef-building corals to understand how hotter ocean temperatures might influence their ability to compete against each other within their coral host. The work builds on decades of research which has honed in on certain types of algal species which confer heat resistance to their host. Why these heat-tolerant species are not more widespread has remained a mystery, until now.

"We know that the ability of corals to withstand warming oceans is related to their microbiome. You could say we are asking the same types of questions as a physician: Can we manipulate the host microbiome to improve coral health? Our paper demonstrates that the efficacy of probiotic treatments or assisted evolution might depend on how these microbes interact with each other" explains postdoctoral fellow Dr Shelby McIlroy who co-led the study with PhD student Jane Wong.

The experiments were conducted at two temperatures; a heated treatment to simulate a coral bleaching event and an unheated control. The researchers found that the heat-tolerant algae were poor competitors at both temperatures and adopted a "shelter-in-place" strategy by storing more fats and carbohydrates to persist through times of stress. At normal temperatures, the thermally sensitive species grew similarly whether the other species was present or not. However, with warming competition triggered a marked increase in resource consumption, essentially restricting the availability of growth resources to its competitors. What the researchers suggest is that thermally tolerant algae have failed to become more widespread because they are outcompeted in most scenarios and simply the "last-man standing" under conditions unsuitable for other species.

The researchers combined three established methods - Fluorescent In-Situ Hybridization (FISH), Flow Cytometry (Flow), and Stable Isotope Analysis (SIA) - to differentiate two species of algae from one another that were grown together in a mixed culture. After introducing isotopically labeled nutrients, the team allowed the cells to assimilate carbon and nitrogen prior to separating them for isotope analysis. In this way they could see if one species was obtaining more resources for growth and reproduction than the other - evidence of competition. They called the method FFS.

"FFS is an exciting marriage of established methods. We applied it to an interesting question related to corals, but it can be adapted for any microbial community - such as the human gut. In doing so we can begin to assign metabolic functions to certain bacteria which are known to be present and may express certain genes but whose actual function remains unknown." said Dr David Baker, Associate Professor of School of Biological Sciences and Swire Institute of Marine Science who supervised the study.

A new study reports the highest efficiency ever recorded for full roll-to-roll printed perovskite solar cells (PSCs), marking a key step on the way to cheaper and more efficient ways of generating solar energy.

A team at Swansea University's SPECIFIC Innovation and Knowledge Centre, led by Professor Trystan Watson, has reported using a roll-to-roll fabrication method for four layers of slot-die coated PSCs.

The PSCs gave the stable power output of 12.2% - the highest efficiency recorded for four layers of roll-to-roll printed PSCs to date.

A newcomer to the photovoltaic industry, PSCs have gathered remarkable attention from researchers around the globe. With efficiency reaching similar levels to those of silicon photovoltaics (PV), the current market leader, attention has been diverted towards upscaling PSCs.

In contrast to silicon PV, which requires high temperature and high vacuum depositions, PSCs can be solution-processed at a low temperature, which significantly reduces the manufacturing cost.

Low temperature processing makes it possible to use plastic substrates to create flexible solar cells.

The ability to solution-process provides the opportunity to apply various well-developed printing and coating techniques:

Screen printing

Inkjet printing

Gravure printing

Slot-die coating

Spray coating

These advantages made it possible for Swansea University researchers to use roll-to-roll manufacturing for four layers of PSCs.

Slot-die coating provides several advantages over the alternatives: it is a pre-metred technique, which means the wet film thickness can be controlled before coating. It is also highly efficient in material usage, with minimal loss of material compared with spray coating or screen printing.

Using the necessary toxic solvents at an industrial scale requires a lot of air handling to stay under the safety limits, which can incur significant and unnecessary expenses. For this reason, an acetonitrile-based system was used. This system has a rheological advantage due to low viscosity and low surface tension, which results in better coatings.

Along with this, a ternary blend of high workplace exposure limit solvents was introduced, replacing chlorobenzene for the deposition of hole transport material. In this research, the PSCs gave the stable power output of 12.2%, which is the highest efficiency reported for four layers of roll-to-roll printed PSCs.

A complete solar cell for a chosen architecture requires coating five layers. In this case, four layers were coated using slot-die coating and the top contact was put on using thermal evaporation. Slot-die coating the fifth (top) contact without destroying any layers underneath has not yet been achieved. Solving this would enable the manufacture of a fully roll-to-roll printed PSC.

Rahul Patidar of SPECIFIC, lead researcher on the project, said:

"Perovskite solar cells aim to increase the efficiency and lower the cost of traditional solar energy generation. They have the potential to be highly efficient and relatively cheap to manufacture, so the aim is to improve fabrication methods for upscaling.

This study signifies the next step towards commercialisation."

Our immune system ought to be able to recognize and kill tumor cells. However, many tumors deceive the immune system. For example, they induce the so-called immune checkpoints of T-cells to shut down immune responses. In the journal Angewandte Chemie, scientists have now introduced a new approach for immunological tumor treatment. Their method is based on the specific blockade of an immune checkpoint by a stable "mirror-image" peptide.

T lymphocytes have a variety of immune checkpoints on their surface, some that crank up the immune system and others that suppress immune reactions when they "discover" suitable ligands on the surfaces of "checked" cells. One such immune checkpoint is the programmed cell death protein 1 (PD-1). If the PD-L1 ligand is bound to PD-1, the immune response is inhibited to prevent attack on healthy cells produced by the body. Unfortunately, many tumors "camouflage" themselves with a particularly large number of PD-L1, which protects them. Blocking the interaction between PD-1 and PD-L1 can normalize the cancer immunity in the microenvironment around tumors. However, previous therapeutic approaches had only limited success, and the tumors often developed resistance.

A newly discovered immune checkpoint known as TIGIT could provide an alternative point of attack. TIGIT reacts to a ligand named PVR with an immunosuppressive signal. A team of researchers at Zhengzhou University in Zhengzhou, Tsinghua University in Beijing, and Sun Yat-sen University in Shenzhen, led by Yanfeng Gao and Lei Liu used RNA expression data from the Cancer Genome Atlas and Gene Expression Omnibus dataset to discover that TIGIT is much more common than PD-1 in many tumors, including those resistant to anti-PD-1 therapy.

The researchers wanted to use a peptide as their new drug because these molecules penetrate more deeply into tissue with affinities and specificities equal to those of antibodies. They cause significantly fewer undesired immunological side effects and are easier to produce. Their disadvantage is that they are rapidly broken down by proteases in the body. For this reason, the researchers decided to use "mirror-image" peptides, which are stable toward proteases. Amino acids can exist in the natural L configuration, or its mirror image, the synthetic D configuration. D peptides made from D amino acids are significantly more long-lived than L peptides.

To find a suitable peptide, the researchers used the mirror-image phage display technique. In this method, very large numbers of different biotechnologically produced peptides are presented on the surfaces of phages (viruses that attack bacteria). Those that bind to the desired target molecule are then selected and multiplied in bacteria. They then go through further selection cycles until only very strongly binding peptides remain. Initially, L peptides are presented in mirror-image phage display. However, those selected bind to the mirror image of the target molecule. For this, the researchers synthesized a portion of TIGIT in the D configuration. As the last step, they produced the mirror-image D version of the strongest binding L peptide, which fitted the key binding interface of the TIGIT/PVR protein perfectly.

The D-peptide known as (D)-TBP-3 developed by this technique effectively blocks the interaction of TIGIT with PVR, is stable toward proteases, and inhibits the growth and metastasis of anti-PD-1 resistant tumor models.

The seafood industry requires large amounts of water for food processing. Before used water is discharged, some organic matter, including protein, is typically removed. This sludge is usually landfilled or converted into biogas, which results in the valuable nutrients it contains being lost from the food chain. Now researchers report in ACS Sustainable Chemistry & Engineering a method to recover these nutrients from shrimp processing water so they can be incorporated in food or feed.

At present, food processing factories remove organic matter from water by first clumping it together with chemical treatments (coagulation) and then raising those clumps to the surface with a technique such as "dissolved air flotation" (DAF). Coagulation is traditionally carried out with iron or other non-food-grade flocculants that clean the water efficiently, but render the removed sludge unsuitable for food or feed purposes. One alternative is to filter the nutrients from the water using membranes, but the equipment is expensive and can clog. A more sustainable option is to switch to food-grade flocculants in combination with DAF. Although a few other studies have shown that such a combination could work, these were small-scale experiments. Ingrid Undeland and Bita Forghani of Chalmers University of Technology and colleagues wanted to scale up the combined food-grade flocculation-DAF process and assess the nutrient composition of the recovered biomass.

At a processing plant, the team treated shrimp processing water with alginate or carrageenan, edible flocculants derived from seaweed. The resulting particles were then collected via DAF and dried. The combination technique captured up to 98% of the protein present in the water, considerably more than flotation alone could collect. The recovered shrimp biomass contained up to 61% proteins and 23% total lipids. The researchers concluded the process could be used for recovering nutrients from shrimp processing water for later use in food or feed. 

Researchers affiliated with the Genomics for Climate Change Research Center (GCCRC), hosted by the University of Campinas (UNICAMP) in the state of São Paulo, Brazil, have discovered a protein involved in corn's resistance to dry weather, high temperatures, and fungal invasion.

This finding paves the way for the development of more drought-resistant plants and products that reduce losses in production at a time when global climate change threatens crop yields around the world. An article on the study is published in BMC Plant Biology.

The GCCRC is an Engineering Research Center (ERC) established by FAPESP and the Brazilian Agricultural Research Corporation (EMBRAPA).

The researchers named the new protein drought-responsive inactive kinase 1 (DRIK1). They also found a synthetic molecule that binds to DRIK1 and can be used in the future to breed plants in which the activity of the protein is naturally reduced or to develop products that inhibit the protein.
"Under normal conditions, the protein controls the plant's developmental mechanisms and inhibits stress-response genes. In dry weather or when the plant is attacked by pathogens, levels of the protein are reduced, and the necessary response is triggered to control the effects of water stress, thermal stress or pathogen attack," said Paulo Arruda (http://www.fapesp.br/cpe/home), a professor in UNICAMP's Institute of Biology (IB) and GCCRC's project leader.

To identify the molecule that binds to the protein, the researchers used a platform developed by UNICAMP's Center for Medicinal Chemistry (CQMED) to discover molecular targets for drugs. Led by Arruda, CQMED is also one of the National Science and Technology Institutes (INCTs) co-funded in the state of São Paulo by São Paulo Research Foundation - FAPESP and the National Council for Scientific and Technological Development (CNPq).

"CQMED's platform can search libraries for small molecules that inhibit specific proteins," Arruda explained. "In human health, this is important for the development of a new drug that inhibits a kinase protein involved in a disease, for example. We used the platform to identify a molecule that binds to the plant's protein kinase, and now we can study the function of the water stress response mechanism in which it is involved."

The researchers screened a library of 378 compounds that might bind to DRIK1 and identified a synthetic molecule with this capacity (ENMD-2076). They plan to modify it so that it can regulate DRIK1, increasing or decreasing its expression in plants.

The authors of the article also include Bruno Aquino, who worked as a postdoctoral intern at IB-UNICAMP with a scholarship from FAPESP; Viviane Cristina Heinzen da Silva, currently a postdoctoral intern in UNICAMP's Center for Molecular Biology and Genetic Engineering (CBMEG); and Katlin Brauer Massirer, CQMED's coprincipal investigator with Arruda.

Water stress response

To find the protein DRIK1, scientists searched a public database for genes related to the response to water stress in plants. They grew corn from seeds in a plant growth chamber for 15 days, watering some of the plants normally throughout the period. The others were divided into three groups and were not irrigated for nine, 12 or 14 days.

Samples of leaves and roots were RNA-sequenced. The researchers found that the water-stressed plants expressed less DRIK1 but that levels of the protein returned to normal when the plants were watered.

Information mined from the same database showed that DRIK1 probably behaves similarly in response to warmer temperatures and attacks by at least two different fungi.

The researchers also analyzed the protein's three-dimensional structure and mapped potentially important regions for the stress response function. In the future, these regions could serve as targets for compounds that modulate the protein's action mechanism.

Researchers are now working on the production of plants genetically engineered for altered expression of DRIK1 with the aim of obtaining varieties that are more drought-resistant.

"If we succeed in producing a variety that withstands water stress slightly more than others during a drought, it will be like having genetic insurance," Arruda said. "There will always be losses, but tons of food will be saved if these losses can be reduced."

Researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) have revealed the evolutionary history of the crown-of-thorns starfish - a predator of coral that can devastate coral reefs. Their findings shed light on how the populations of these starfish have changed over time and could potentially help reduce their ecological destruction.

A single crown-of-thorns starfish is formidable, with a large body covered in spiky, venomous thorns. But their true danger lies in their potent reproductive ability, with female crown-of thorns starfish releasing millions of eggs in a single spawning. This can quickly lead to plagues, with uncontrollably large numbers of starfish rapidly destroying vast areas of coral reef.

"Almost 40 years ago, Okinawa experienced a massive outbreak of crown-of-thorns starfish, where over 1.5 million starfish had to be removed by divers by hand," said Professor Noriyuki Satoh, senior author of the student and leader of the Marine Genomics Unit at OIST.

Although outbreaks have recently become less frequent around Okinawa and other subtropical islands in the Ryukyu Archipelago, they have become an increasingly large threat to the Great Barrier Reef in Australia, along with coral bleaching and tropical cyclones. These starfish outbreaks are becoming more common and more severe, as increasingly polluted and warmer waters aid the survival of the larvae.

In 2017, the OIST Marine Genomics Unit teamed up with Australian scientists to decode the genome of the crown-of-thorns starfish, with their results published in Nature. Now, in their latest study published in G3: Genes|Genomes|Genetics, the Marine Genomics Unit wanted to explore whether any information was recorded in the starfish genomes that could shed light on how and why these outbreaks occur.

The researchers collected crown-of-thorns starfish from coral reefs around three different islands in the Ryukyu Archipelago - Okinawa, Miyako and Iriomote. The scientists then sequenced the entire DNA found in the mitochondria, comprised of over 16,000 nucleotide bases, and used differences in the sequences between the individual starfish to construct an evolutionary tree.

The unit also performed the same analyses on two other starfish species - the blue starfish and the northern Pacific sea star. By comparing the crown-of-thorns starfish to these other two species, the scientists hoped to see whether their findings revealed anything unique to the crown-of-thorns starfish.

"The blue starfish is also a coral reef predator that lives in the same habitat as the crown-of-thorns starfish, but it doesn't produce these uncontrollable outbreaks," said Prof. Satoh. "Meanwhile, the northern Pacific sea star is the most common starfish in Japan and lives in colder waters around the Japanese mainland."

The scientists found that the evolutionary tree for the northern Pacific sea star showed that the species had split into two major lineages. Starfish collected from three different locations in the seas around the north-eastern regions of Japan were composed of individuals from one lineage, whilst a single population in the Seto Inland Sea in south-west Japan was formed of individuals from a second, more recent lineage.

"We believe that in a rare migration event, starfish larvae dispersed to the Seto Inland Sea. As these two areas are so separated, no migration occurred afterwards between the two populations, which resulted in the species splitting into two lineages," said Prof. Satoh. "Meanwhile, shorter range ocean currents kept individuals from the first lineage mixed between the nearby locations in the north-east of Japan."

For the blue starfish, the results were more surprising. The constructed evolutionary tree showed that the species had first split into two lineages, with the second lineage then diverging again into two smaller subgroups. But intriguingly, individuals from the two major lineages were found in both Okinawa and Ishigaki - the two areas in the Ryukyus where the blue starfish was collected. This means that two distinct starfish populations are living in the same geographic regions but are not breeding and mixing their genes. Prof. Satoh believes that this is strong evidence for there being two cryptic species of blue starfish - in other words, the starfish look the same despite being separate, non-breeding species.

The results also suggest that blue starfish migration occurs in both directions between Okinawa and Ishigaki. This was unexpected as the scientists had previously assumed that the powerful northeastern current flowing from Ishigaki towards Okinawa prevented starfish larvae from being carried in the opposite direction.

"For migration to readily occur in both directions, this suggests that the ocean currents in the Ryukyu Archipelago may be more complex that previously imagined," said Prof. Satoh.

The results from the evolutionary tree of the crown-of-thorns starfish also supported the idea of complex ocean currents in the region, with each crown-of-thorns starfish lineage also found in more than one geographic location. This has important implications for predicting where new outbreaks of crown-of-thorns starfish may occur in the Ryukyus, with the researchers now advocating for better understanding of the ocean currents in the area.

Overall, the evolutionary tree for the crown-of-thorns starfish looked significantly different from the other two starfish, underlying key differences in the species' historical population dynamics. Despite being a much younger species than the other two species, diverging less than one million years ago, the tree showed that the starfish quickly fragmented into five small lineages. These findings suggest that the species underwent frequent genetic bottlenecks, where the population was reduced to just a small number of individuals, which then jumpstarted a new lineage.

"This implies that the starfish outbreaks are just one part of a larger 'boom and bust' population cycle, where if they are left to their natural devices, the starfish eat so much coral that they run out of food and die," said Prof. Satoh.

For their next steps, the Marine Genomics Unit is collaborating with Australian scientists to analyze crown-of-thorns starfish from the Great Barrier Reef. Instead of just using DNA in the mitochondria, the scientists aim to sequence the entire genome of each starfish, including DNA in the nucleus.

"Ultimately, we hope our findings can help us understand the population trends of the starfish better and the role of ocean currents in seeding new outbreaks," concluded Prof. Satoh. "This could potentially help us predict and therefore mitigate future outbreaks."

An organisation that is required by national law to have significant female representation on its board of directors sees higher diversity and skills than those in countries that simply advise on quotas, according to research from City, University of London's Business School.

Dr Sonia Falconieri, Reader in Finance and Chiara De Amicis, PhD in Finance student at City, along with Dr Moez Bennouri from Montpellier Business School, studied the boards of British, French and Italian listed companies across a 14-year period.

Each country has its own respective laws on gender quotas as follows:

United Kingdom - a soft, voluntary ratio of at least 25 per cent female representation on FTSE100 boards was recommended by the Davies Report of 2011, later amended to 33 per cent in 2015. FTSE250 were also advised to achieve this by 2020.

France - gender quotas implemented in 2011 required listed and non-listed companies of more than 500 employees and revenues above 50 million Euros to have a minimum of 20 per cent female representation on their boards of directors, which rose to 40 per cent in 2014. Failure to comply incurs voided appointments to the board and suspended payment of attendance.

Italy - quotas came into law in 2012 requiring publicly listed companies to have at least 20 per cent of either gender on first renewal of their board of directors, and 33 per cent after the second renewal. Failure to comply results in large fines and even potential voiding of directorships.

The research found that introduction of regulation was the single largest catalyst for an increase in the presence of women on boards, with this felt significantly more sharply in France and Italy under mandatory rather than voluntary regimes. The data collected also showed a marked increase in compliance with these guidelines.

Another study carried out to determine the 'quality' of these boards under gender quota guidelines showed no deterioration in cases of high diversity, and in several cases improved where quotas were mandatory.

Dr Falconieri said:

"Boardroom diversity is crucial to the success and sustainability of an organisation.

"There is a risk that the current pandemic crisis could see countries that do not enforce quotas on gender diversity take a large backwards step in terms of female representation in the boardroom.

"Our study demonstrates that businesses are more compliant with gender diversity regulation if it is enforced. In addition to this, we find no evidence to suggest that the quality of boardrooms, normally associated with effective monitoring, deteriorates under this mandatory regulation.

"Despite this, gender quota regulations have not yet had an overall positive impact on the appointment of female executives or board chairs, which remains a great challenge and an obstacle to gender equality."

MANHATTAN, KANSAS -- Several species of fish have adapted to harsh environments using the same mechanism, which brings to question evolutionary chance, according to a study by Kansas State University and Washington State University.

Michi Tobler, associate professor, Ryan Greenway, May 2019 doctoral graduate, and Nick Barts, doctoral student, all in the Division of Biology; Joanna Kelley, associate professor at Washington State University; and many additional collaborators recently published an article about repeated adaptations to extreme environments in Proceedings of the National Academy of Sciences.

"We are trying to understand how evolution and adaptation work," Tobler said. "We stumbled across these fish living in this highly toxic water. It is so toxic that it kills most other living things by binding to an enzyme in the mitochondria -- the powerhouse of cells -- and shuts off energy production at the cellular level."

The streams have high concentrations of hydrogen sulfide, a gas that is naturally dissolved in the water. Tobler and his collaborators found at least 10 different lineages of fish that have adapted to live in the extreme environment.

"Whether or not populations take the same path to adapting to novel environments is a long-standing question in evolutionary biology," Kelly said. "Our research shows that the same pathways have been modified in multiple different species of hydrogen sulfide adapted fishes."

All 10 adapted, regardless of location, using the same mechanism: tweaking the enzyme so the toxicant can't bind to it.

"The cool thing about these enzymes is all organisms have them," Tobler said. "We have them. Fungi have them. Plants have them. It's the universal way to make energy. Yet, it is this ancient pathway that has been conserved for so long that is modified in these fish."

According to Tobler, the fish also ramped up an existing detoxification mechanism inside the mitochondria so they can get rid of the hydrogen sulfide faster and survive when other non-adapted fish in the same species can't survive in the toxic water. The multiple lineages of fish with this capability brings to question a view proposed by evolutionary biologist Stephen Gould, that if evolution repeated itself, it would lead to different outcomes every time.

"Thirty years ago, Gould said 'if you could rewind the tape of life, you would get a different outcome every single time,' meaning that evolution would not find the same adaptive solutions every time," Tobler said. "What we actually found in all these lineages -- where the tape of life has been replayed as they were exposed to the same sources of selection -- is that evolution actually unfolds in very similar ways. I think it tells us something very fundamental about how organisms adapt and that adaptive solutions are possibly limited."

The researchers are able to compare the fish with the adaptation living the toxic water with ancestors that live in the normal environment because there is not a barrier between habitats. Tobler said as a consequence of the fish adapting to the toxic environment, they are actually evolving into a new species. His graduate students have further research pending.

ORLANDO, July 8, 2020 - The National Science Foundation's Arecibo Observatory in Puerto Rico has proven itself instrumental in another major astronomical discovery.

An international team of scientists, led by the University of East Anglia in the United Kingdom, found an asymmetrical double neutron star system using the facility's powerful radio telescope. This type of star system is believed to be a precursor to merging double neutron star systems like the one that LIGO/Virgo (the Laser Interferometer Gravitational-Wave Observatory in the United States) discovered in 2017. The LIGO/Virgo observation was important, because it confirmed the gravitational waves associated with merging neutron stars.

The work published by this team today in the journal Nature, indicates these specific kinds of double neutron star systems may be the key to understanding dead star collisions and the expansion of the universe.

"Back in 2017, scientists at LIGO/Virgo first detected the merger of two neutron stars," says physicist Robert Ferdman, who led the team. "The event caused gravitational-wave ripples through the fabric of space time, as predicted by Albert Einstein over a century ago. It confirmed that the phenomenon of short gamma-ray bursts was due to the merger of two neutron stars."

One of the unique aspects of the 2017 discovery and today's is that the double neutron systems observed are composed of stars that have very different masses. Current theories about the 2017 discovery are based on the masses of stars being equal or very close in size.

"The double neutron star system we observed shows the most asymmetric masses amongst the known merging systems within the age of the universe," says Benetge Perera, a UCF scientist at Arecibo who co-authored the paper. "Based on what we know from LIGO/Virgo and our study, understanding and characterizing of the asymmetric mass double neutron star population is vital to gravitational wave astronomy."

Perera, whose research is focused on pulsars and gravitational waves, joined the NSF-funded Arecibo Observatory in June 2019. The facility, which is managed by the University of Central Florida through a cooperative agreement with the NSF, offers scientists around the world a unique look into space because of its specialized instruments and its location near the equator.

The Discovery

The team discovered an unusual pulsar - one of deep space's magnetized spinning neutron-star 'lighthouses' that emits highly focused radio waves from its magnetic poles.

The newly discovered pulsar (known as PSR J1913+1102) is part of a binary system - which means that it is locked in a fiercely tight orbit with another neutron star.

"The Arecibo Observatory has a long legacy of important pulsar discoveries," says NSF Program Officer, Ashley Zauderer. "This exciting result shows how incredibly relevant the facility's unique sensitivity remains for scientific investigations in the new era of multi-messenger astrophysics."

Neutron stars are the dead stellar remnants of a supernova explosion. They are made up of the densest matter known - packing hundreds of thousands of times the Earth's mass into a sphere the size of a city like New York.

In about half a billion years the two neutron stars will collide, releasing astonishing amounts of energy in the form of gravitational waves and light.

That collision is what the LIGO/Virgo team observed in 2017. The event was not surprising, but the enormous amount of matter ejected from the merger and its brightness was unexpected, Ferdman said.

"Most theories about this event assumed that neutron stars locked in binary systems are very similar in mass," Ferdman says. "But this newly discovered binary is unusual because the masses of its two neutron stars are quite different - with one far larger than the other. Our
discovery changes these assumptions."

This asymmetric system gives scientists confidence that double neutron star mergers will provide vital clues about unsolved mysteries in astrophysics - including a more accurate determination of the expansion rate of the universe, known as the Hubble constant.

One of the emerging questions about the coronavirus that scientists are working to understand is why developing countries are showing markedly lower rates of mortality in COVID-19 cases than expected.

Research by Assistant Professor Luis Escobar of the College of Natural Resources and Environment and two colleagues at the National Institutes of Health suggests that Bacille Calmette-Guérin (BCG), a tuberculosis vaccine routinely given to children in countries with high rates of tuberculosis infection, might play a significant role in mitigating mortality rates from COVID-19. Their findings have been published in the Proceedings of the National Academy of Sciences.

"In our initial research, we found that countries with high rates of BCG vaccinations had lower rates of mortality," explained Escobar, a faculty member in the Department of Fish and Wildlife Conservation and an affiliate of the Global Change Center housed in the Fralin Life Sciences Institute. "But all countries are different: Guatemala has a younger population than, say, Italy, so we had to make adjustments to the data to accommodate those differences."

Escobar, working with NIH researchers Alvaro Molina-Cruz and Carolina Barillas-Mury, collected coronavirus mortality data from around the world. From that data, the team adjusted for variables, such as income, access to education and health services, population size and densities, and age distribution. Through all of the variables, a correlation held showing that countries with higher rates of BCG vaccinations had lower peak mortality rates from COVID-19.

One sample that stood out was Germany, which had different vaccine plans prior to the country's unification in 1990. While West Germany provided BCG vaccines to infants from 1961 to 1998, East Germany started their BCG vaccinations a decade earlier, but stopped in 1975. This means that older Germans -- the population most at risk from COVID-19 -- in the country's eastern states would have more protection from the current pandemic than their peers in western German states. Recent data shows this to be the case: western German states have experienced mortality rates that are 2.9 times higher than those in eastern Germany.

"The purpose of using the BCG vaccine to protect from severe COVID-19 would be to stimulate a broad, innate, rapid-response immunity," said Escobar, who noted that the BCG vaccines have already been shown to provide broad cross-protections for a number of viral respiratory illnesses in addition to tuberculosis.

Escobar stresses that the team's findings are preliminary, and that further research is needed to support their results and determine what the next steps should be for researchers. The World Health Organization noted that there is no current evidence that the BCG vaccine can protect people from COVID-19 infections, and stated that it does not currently recommend BCG vaccinations for the prevention of COVID-19. There are currently clinical trials underway to establish whether BCG vaccination in adults confers protection from severe COVID-19.

"We're not looking to advise policy with this paper," Escobar said. "This is, instead, a call for more research. We need to see if we can replicate this in experiments and, potentially, in clinical trials. We also need to come back to the data as we get more information, so we can reevaluate our understanding of the coronavirus pandemic."

Barillas-Mury, a chief researcher who specializes in mosquito-borne disease vectors, noted that establishing a link between BCG vaccines and COVID-19 case severity could result in attempts to stockpile doses of the BCG vaccine, placing countries with high tuberculosis rates at risk.

"If the BCG vaccine is protective, production would have to increase to meet the sudden spike in vaccine demand in order to prevent a delay in distribution to countries that very much need it to fight tuberculosis," she said.

While a direct correlation between BCG vaccinations and a reduction in coronavirus mortalities still needs to be understood more fully, researchers hold hope that the BCG vaccine might be able to provide at least short-term protections against severe COVID-19, particularly for front-line medical workers or high-risk patients. And, if BCG does provide short-term protection, there are longer term considerations about how countries could best utilize BCG vaccines to reduce mortality rates for future viral outbreaks that target the human respiratory system.