Culture

The two major types of cetaceans appear to have evolved their characteristic blowholes through different anatomical transformations, according to a study being presented at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30.

Cetaceans, a group of marine mammals that includes whales and dolphins, evolved from ancestors that walked on land around 50 million years ago. Somewhere along the way, the forward-pointing nose shifted to an upward-pointing blowhole, making it easier for the animals to breathe air while swimming.

For the new study, researchers observed shifts in nasal passage orientation in spotted dolphin and fin whale embryos and fetuses. Both species initially develop a forward-pointing nose, like any other mammal, which gradually transforms into a blowhole by birth. Anatomical changes during prenatal development can provide clues about how certain traits evolved over time.

"The main difference we observed is in how the nostrils reach this position during prenatal development -- there does not seem to be one way to do it," said Rachel Roston, PhD, a postdoctoral fellow at the University of Washington and the study's lead author. "The dolphin species and other toothed whales showed backwards bending of the skull, whereas the fin whale and other baleen whales showed changes in the occipital bone at the back of the skull."

Researchers have previously studied other differences in the nasal passages of the two types of cetaceans; for instance, toothed whales have a single nostril whereas baleen whales have two. By focusing on the part of the skull that connects the nasal passage and the rest of the body, the new study examines previously unexplored territory at the intersection of nasal passage orientation and head-body alignment.

Roston says the work suggests that the two cetacean types may have evolved their blowholes through different developmental processes, though additional research, such as studies of the fossil record, would be needed to more rigorously test this hypothesis.

"Few, if any, other mammals have evolved such an extreme shift in nasal passage orientation and nostril position," said Roston. "Understanding how developmental transformations lead to nasal passage reorientation during prenatal development helps us understand how changes to development can lead to the evolution of extreme and unique anatomical features."

Roston will present this research in poster R4523 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

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Using a newly developed mouse model of acute lung injury, researchers found that exposure to the SARS-CoV-2 spike protein alone was enough to induce COVID-19-like symptoms including severe inflammation of the lungs.

SARS-CoV-2, the virus that causes COVID-19, is covered in tiny spike proteins. These proteins bind with receptors on our cells, starting a process that allows the virus to release its genetic material into a healthy cell.

"Our findings show that the SARS-CoV2 spike protein causes lung injury even without the presence of intact virus," said Pavel Solopov, PhD, DVM, research assistant professor at the Frank Reidy Research Center for Bioelectrics at Old Dominion University. "This previously unknown mechanism could cause symptoms before substantial viral replication occurs."

Solopov will present the new research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

Studying SARS-CoV-2 can be challenging because experiments involving the intact virus requires a Biosafety Level 3 laboratory. To overcome this hurdle, the researchers created a new model of acute lung injury that utilizes transgenic mice that express the human receptor for SARS-CoV-2 in their lungs.

"Our mouse model dramatically reduces the danger of doing this type of research by allowing COVID-19 lung injury to be studied without using the intact, live virus," said Solopov. "This will greatly increase and diversify the ability to do COVID-19 research. Our model will also likely be useful for studying other coronaviruses."

The researchers injected the genetically modified mice with a segment of the spike protein and analyzed their response 72 hours later. Another group of mice received only saline to serve as a control.

The researchers found that the genetically modified mice injected with the spike protein exhibited COVID-19-like symptoms that included severe inflammation, an influx of white blood cells into their lungs and evidence of a cytokine storm - an immune response in which the body starts to attack its own cells and tissues rather than just fighting off the virus. The mice that only received saline remained normal.

"These findings show that the genetically modified mouse together with just a segment of the spike protein can be used to study SARS-CoV-2 lung injury," said Solopov. "We can use this tool to develop a better understanding of how the spike protein causes lung symptoms -- even without the intact virus -- in order to develop new targets and therapeutics for COVID-19."

The researchers plan to continue this line of investigation by using the new mouse model to study the effectiveness of several drugs in reducing the severity of acute lung injury and COVID-19.

Pavel Solopov will present during an on-demand presentation (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

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A technology-packed tank top offers a simple, effective way to track astronauts' vital signs and physiological changes during spaceflight, according to research being presented at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30.

By monitoring key health markers over long periods of time with one non-intrusive device, researchers say the garment can help improve understanding of how spaceflight affects the body.

"Until now, the heart rate and activity levels of astronauts were monitored by separate devices," said Carmelo Mastrandrea, PhD, a postdoctoral fellow at the Schlegel-University of Waterloo Research Institute for Aging in Canada, and the study's first author. "The Bio-Monitor shirt allows simultaneous and continuous direct measurements of heart rate, breathing rate, oxygen saturation in the blood, physical activity and skin temperature, and provides a continuous estimate of arterial systolic blood pressure."

The Bio-Monitor shirt was developed for the Canadian Space Agency by Carré Technologies based on its commercially available Hexoskin garment. In a study funded by the Canadian Space Agency, a team of researchers from the Schlegel-University of Waterloo Research Institute for Aging oversaw the first test of the shirt in space for a scientific purpose. Astronauts wore the shirt continually for 72 hours before their spaceflight and 72 hours during spaceflight, except for periods of water immersion or when the device conflicted with another activity.

The shirt's sensors and accelerometer performed well, providing consistent results and a large amount of usable data. Based on these initial results, researchers say the shirt represents an improvement over conventional methods for monitoring astronauts' health, which require more hands-on attention.

"By monitoring continuously and non-intrusively, we remove the psychological impacts of defined testing periods from astronaut measurements," said Mastrandrea. "Additionally, we are able to gather information during normal activities over several days, including during daily activities and sleep, something that traditional testing cannot achieve."

In flight, the astronauts recorded far less physical activity than the two and a half hours per day recorded in the monitoring period before takeoff, a finding that aligns with previous studies showing large reductions in physical activity during spaceflight. In addition to monitoring astronauts' health and physical activity in space, Mastrandrea noted that the shirt could provide early warning of any health problems that occur as their bodies re-adapt to gravity back on Earth.

The commercial version of the Bio-Monitor shirt is available to the public, where it can be used for various applications including assessing athletic performance and monitoring the health of people with limited mobility. In addition to spaceflight, researchers are examining its potential use in other occupational settings that involve extreme environments, such as firefighting.

Mastrandrea will present this research in poster R2888 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

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New research offers an up-close view of how SARS-CoV-2, the virus that causes COVID-19, can spread to the brain. The study helps explain the alarming array of neurological symptoms reported in some patients with COVID-19, as well as why some patients suffer severe neurological effects while others experience none at all.

The researchers report evidence that SARS-CoV-2 can infect both the nerve cells that power our brains (neurons), and the cells in the brain and spinal cord that support and protect neurons (astrocytes).

"Our findings suggest that astrocytes are a pathway through which COVID-19 causes neurological damage," said Ricardo Costa, PhD, a postdoctoral fellow at the Louisiana State University (LSU) Health Shreveport and the study's first author. "This could explain many of the neurologic symptoms we see in COVID-19 patients, which include loss of sense of smell and taste, disorientation, psychosis and stroke."

Costa will present the research at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. The study is led by Diana Cruz-Topete, assistant professor of molecular and cellular biology at LSU Health Shreveport, and includes collaborators Oscar Gomez-Torres, PhD, and Emma Burgos-Ramos, PhD, from Universidad de Castilla-La Mancha in Spain.

In the respiratory system, SARS-CoV-2 is known to infect a person's cells by grabbing hold of proteins on the cell surface called angiotensin-converting enzyme-2 (ACE2) receptors. It has been unclear whether brain cells have this receptor.

For the study, Costa and colleagues examined RNA and proteins to determine whether cell cultures of human astrocytes and neurons expressed ACE2. They then exposed the cells to a version of the SARS-CoV-2 virus that had been modified to be safe for researchers to handle. The studies confirmed that both astrocytes and neurons express the ACE2 receptor and that both cell types can become infected with SARS-CoV-2, though astrocytes were less likely to become infected.

Astrocytes are the main gateway to the brain, responsible for shuttling nutrients from the bloodstream to the neurons while keeping harmful particles out. By resisting infection, astrocytes could help keep SARS-CoV-2 out of the brain, but once infected, they could easily pass the virus along to many neurons, according to researchers.

"While astrocytes display a higher resistance to infection, neurons seem to be more susceptible," said Costa. "This suggests that only few astrocytes getting infected could be sufficient for the infection to quickly spread to neurons and multiply quickly. These observations could explain why while some patients do not have any neurological symptoms, others seem to have severe ones."

Costa will present this research from 3:15-3:30 p.m. Tuesday, April 27 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

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New insights into how fetal and adult liver cells differ could be used to help make liver cell transplants successful long term. Transplanting functioning liver cells into a patient's liver can help replace liver function that is impaired due to disease.

Today there are many more patients waiting for liver transplants than there are donor organs available. Because liver cell transplantation only requires a portion of cells isolated from a liver, it could allow multiple patients to be treated from one donated organ.

Although liver cell transplants offer a promising life-saving alternative to transplanting the whole organ, the effects aren't long-lasting when adult liver cells are used. Clinical trials and animal studies have shown that when fetal liver cells are used for liver cell transplants, they multiply and maintain function for long periods of time. However, fetal liver cells cannot be readily obtained for clinical use.

"Our work aims to characterize the mechanisms by which fetal liver cells -- or hepatocytes -- repopulate an injured adult liver," said Anders Ohman, a doctoral candidate in the laboratory of Jennifer Sanders, PhD, at Brown University. "We can then use this information to develop novel culture conditions and therapeutic strategies that can make liver cell transplantation feasible."

Ohman will present the research at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

To better understand why fetal hepatocytes maintain their function, the researchers transplanted fetal rat hepatocytes into the spleen of mice that had part of their liver removed. Over 10 months, the fetal cells regenerated the liver and made up an increasing percentage of the organ. The researchers then used a technique called laser capture microdissection to collect normal adult liver tissue as well as tissue derived from the transplanted fetal cells.

"Our analysis of these samples identified a number of fetal characteristics that are durably retained months after transplantation into the adult liver microenvironment," said Ohman. "We also found gene expression and cellular processes that are distinct to the fetal-cell-derived tissue."

Next, the researchers aim to identify specific biological drivers of cell growth and proliferation that are responsible for the competitive advantage that the fetal cells have in repopulating the liver.

Anders Ohman will present the findings in poster R3514 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

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The placenta forms the interface between the maternal and foetal circulatory systems. As well as ensuring essential nutrients, endocrine and immunological signals get through to the foetus to support its development and growth, the placenta must also protect it from the accumulation of potentially toxic compounds. A study from Cécile Demarez, Mariana Astiz and colleagues at the University of Lübeck in Germany now reveals that the activity of a crucial placental gatekeeper in mice is regulated by the circadian clock, changing during the day-night cycle. The study, which has implications for the timing of maternal drug regimens, is published in the journal Development.

The circadian clock translates time-of-day information into physiological signals through rhythmic regulation of downstream genes. In this study, the researchers discover that in the labyrinth zone of the mouse placenta, a tissue functionally equivalent to the human chorionic villi, clock genes are expressed in a 24h rhythm. Importantly, they show that this placental clock is responsible for regulating the expression and activity of ABCB1, a drug efflux transporter with hundreds of known substrates.

An important prediction of this work is that the time-of-day of maternal treatment could be an important factor to consider to avoid non-desirable effects for the foetus during pregnancy.

"Pharmacological treatments are mostly avoided by pregnant women but in certain circumstances there is no other option," says Dr. Mariana Astiz. "An example would be maternal treatment with antiretrovirals (many of which are in fact substrates of ABCB1). So, choosing the correct time of day to take drugs like these might reduce the ammount of drug reaching the baby and hence the possible negative effects in the short and long-term."

Dr. Astiz hopes this study will provide a stimulus to design studies that specifically test hypotheses about the placental circadian clock in humans. "This is definitely a very exciting and rapidly advancing field of research."

OAK BROOK, Ill. - Exercise appears to reduce the long-term risk of bronchiectasis, a potentially serious disease of the airways, according to a study published in the journal Radiology.

Bronchiectasis is characterized by repeated cycles of inflammation and exacerbations that damage the airways, leaving them enlarged, scarred and less effective at clearing mucus. This creates an environment ripe for infections. Risk increases with age and the presence of underlying conditions like cystic fibrosis. There is no cure.

Computed tomography (CT) is used to confirm or rule out the disease in patients with symptoms like shortness of breath and coughing up mucus. Bronchiectasis has also been found on CT in asymptomatic and mildly symptomatic individuals.

Little is known about factors that can reduce the risk of bronchiectasis. While some studies have tied higher levels of cardiorespiratory fitness to a reduced risk of declining lung function and airway diseases, such as chronic obstructive pulmonary disease, its benefits in reducing the risk of bronchiectasis are unknown.

To examine the association between cardiorespiratory fitness and bronchiectasis, researchers analyzed data from the long-running Coronary Artery Disease in Young Adults (CARDIA) study. CARDIA was launched in 1984 across the U.S. to examine the risk factors for coronary artery disease in young adults.

The researchers looked at 2,177 healthy adults who were ages 18 to 30 years at the beginning of the study period. The study participants were followed up over a 30-year period with fitness tests and CT.

"We used year zero and year 20 cardiorespiratory fitness measured as exercise duration on a treadmill and ascertained bronchiectasis on chest CT at year 25," said study lead author Alejandro A. Diaz, M.D., M.P.H., assistant professor of medicine at Harvard Medical School and associate scientist at Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital in Boston. "We assessed whether differences in treadmill duration between year zero and 20 were associated with bronchiectasis on CT at year 25."

Of the 2,177 participants, 209, or 9.6%, had bronchiectasis at year 25. Preservation of cardiorespiratory fitness reduced the odds of bronchiectasis on CT at year 25.

"In an adjusted model, one minute longer treadmill duration between year zero and year 20 was associated with 12% lower odds of bronchiectasis on CT at year 25," Dr. Diaz said. "Having preserved fitness at middle age is associated with lower chances of bronchiectasis."

The researchers pointed to several possible explanations for the relationship between cardiorespiratory fitness and bronchiectasis. For one, a high level of cardiorespiratory fitness is linked with lower levels of systemic inflammation, which might help preserve the health of the airway. Good cardiorespiratory fitness also reduces the risk of certain diseases associated with bronchiectasis, such as asthma and pneumonia. Finally, high fitness levels may improve the ability of the airway to clear mucus.

The researchers observed a higher prevalence of bronchiectasis than found in previous studies. The difference may be explained by the use of CT for detecting bronchiectasis in the new study rather than the physician-based diagnosis used in previous studies.

"This study suggests that bronchiectasis on CT scans might be more frequent than previously thought," Dr. Diaz said. "However, the clinical implications of finding bronchiectasis on CT scans in people with no or mild symptoms remain to be determined."

The researchers are studying bronchiectasis in other populations like smokers to look for features of the airways and lung tissue associated with bronchiectasis flare-ups.

"These results amplify the benefits of fitness to human health when a sedentary lifestyle is a concerning world epidemic," Dr. Diaz said. "It also highlights that fitness might be a tool to preserve lung health. The airways are challenged by what we breathe in every minute, and fitness may help to preserve lung health from injuries."

In an effort to determine the potential for COVID-19 to begin in a person's gut, and to better understand how human cells respond to SARS-CoV-2, the scientists used human intestinal cells to create organoids - 3D tissue cultures derived from human cells, which mimic the tissue or organ from which the cells originate. Their conclusions, published in the journal Molecular Systems Biology, indicate the potential for infection to be harboured in a host's intestines and reveal intricacies in the immune response to SARS-CoV-2.

"Previous research had shown that SARS-CoV-2 can infect the gut," says Theodore Alexandrov, who leads one of the two EMBL groups involved. "However, it remained unclear how intestinal cells mount their immune response to the infection."

In fact, the researchers were able to determine the cell type most severely infected by the virus, how infected cells trigger an immune response, and - most interestingly - that SARS-CoV-2 silences the immune response in infected cells. These findings may shed light on the pathogenesis of SARS-CoV-2 infection in the gut, and indicate why the gut should be considered to fully understand how COVID-19 develops and spreads.

According to Sergio Triana, lead author and a doctoral candidate in EMBL's Alexandrov team, the researchers observed how infected cells seem to start a cascade of events that produce a signalling molecule called interferon.

"Interestingly, although most cells in our mini guts had a strong immune response triggered by interferon, SARS-CoV-2-infected cells did not react in the same way and instead presented a strong pro-inflammatory response," Sergio says. "This suggests that SARS-CoV-2 interferes with the host signalling to disrupt an immune response at the cellular level."

Coronaviruses, including SARS-CoV-2, cause infection by latching on to specific protein receptors found on the surface of certain cell types. Among these receptors is the protein ACE2. Interestingly, the researchers showed that the infection is not explained solely by the presence of ACE2 on the surface of the cells, highlighting our still limited knowledge about COVID-19, even after a year of tremendous research efforts worldwide.

As the disease progressed in the organoids, the researchers used single-cell RNA sequencing, which involves several techniques to amplify and detect RNA. Among these single-cell technologies, Targeted Perturb-seq (TAP-seq) provided sensitive detection of SARS-CoV-2 in infected organoids. Lars Steinmetz's research group at EMBL recently developed TAP-seq, which the researchers combined with powerful computational tools, enabling them to detect, quantify, and compare expression of thousands of genes in single cells within the organoids.

"This finding could offer insights into how SARS-CoV-2 protects itself from the immune system and offer alternative ways to treat it," Lars says. "Further study can help us understand how the virus grows and the various ways it impacts the human immune system."

A research group at the RIKEN Center for Biosystems Dynamics Research (BDR) has discovered molecular events that determine whether cancer cells live or die. With this knowledge, they found that reduced consumption of a specific protein building block prevents the growth of cells that become cancerous. These findings were published in the scientific journal eLife and open up the possibility of dietary therapy for cancer.

A tumor is a group of cancer cells that multiplies--or proliferates--uncontrollably. Tumors originate from single cells that become cancerous when genes that cause cells to proliferate are over-activated. However, because these genes, called oncogenes, often also cause cell death, activation of a single oncogene within a cell is not enough for it to become a cancer cell. This phenomenon is thought to be a "fail-safe" mechanism that prevents cells from easily turning into cancer. For a cell to slip through the cracks and become cancer, several other oncogenes, along with cancer-suppressing genes, need to be activated in a multi-step process. The details of this process were the topic of the new study.

The international research group led by Sa Kan Yoo at RIKEN BDR focused on the oncogene Src and investigated how cell proliferation--oncogenesis--and cell death are regulated in the fruit fly. They showed that Src does not induce cell death as a result of cell proliferation, but instead drives both processes independently and simultaneously. By inhibiting the function of specific genes through RNA interference, the team found that the gene p38 was involved in cell proliferation and the gene JNK was involved in cell death. In addition, they discovered a gene called slpr that simultaneously activates p38 and JNK. "How oncogenes simultaneously promote cell death and cell proliferation has been controversial," says Yoo. "Our major finding was that the oncogene Src promotes cell death and cell proliferation via parallel pathways."

One concept for treating cancer takes advantage of the fail-safe mechanism by inhibiting cell proliferation, but not cell death. To do this, we have to know the molecular players involved in the process. Once the team identified p38 activation as a key step leading to cell proliferation, they realized they could make this concept a reality. After studying what else we know about p38, they realized that its activity can be controlled by nutrients in the diet.

They next set out to test this hypothesis by investigating the relationship between the food fed to fly larvae and cell proliferation. They found that reducing the amount of the amino acid methionine in the diet prevented p38-controlled oncogenesis. "We were excited to find that manipulating the amount of dietary methionine can affect cell proliferation but not cell death," says Yoo. "Currently we don't know whether our finding in flies will translate to cases of human cancer. But, we speculate that it will in particular cases because some human cancers also activate the Src gene.

"We are curious to know how general the mechanism is that we found here. Aside from the Src signaling pathway, we also found that slpr can mediate the signaling pathways controlled by other oncogenes. Finding out how this happens is our next goal."

Since the process of oncogenesis is known to be the same in both fruit flies and mammals, the new findings can help explain how human cancers develop.

How do different parts of the brain communicate with each other during learning and memory formation? A new study by researchers at the University of California San Diego takes a first step at answering this fundamental neuroscience question.

The study was made possible by developing a neural implant that monitors the activity of different parts of the brain at the same time, from the surface to deep structures--a first in the field. Using this new technology, the researchers show that diverse patterns of two-way communication occur between two brain regions known to play a role in learning and memory formation--the hippocampus and the cerebral cortex. The researchers also show that these different patterns of communication are tied to events called sharp-wave ripples, which occur in the hippocampus during sleep and rest.

The researchers published their findings Apr. 19 in Nature Neuroscience.

"This technology has been developed particularly for studying interactions and communications between different brain regions simultaneously," said co-corresponding author Duygu Kuzum, a professor of electrical and computer engineering at the UC San Diego Jacobs School of Engineering. "Our neural implant is versatile; it can be applied to any area of the brain and can enable study of other cortical and subcortical brain regions, not just the hippocampus and cerebral cortex."

"Little is known about how various brain regions work together to generate cognition and behavior," said Takaki Komiyama, a professor of neurobiology and neurosciences at UC San Diego School of Medicine and Division of Biological Sciences, who is the study's other co-corresponding author. "In contrast to the traditional approach of studying one brain area at a time, the new technology introduced in this study will begin to allow us to learn how the brain as a whole works to control behaviors and how the process might be compromised in neurological disorders."

The neural implant is made up of a thin, transparent, flexible polymer strip fabricated with an array of micrometer-sized gold electrodes, onto which platinum nanoparticles have been deposited. Each electrode is connected by a micrometers-thin wire to a custom-printed circuit board. Kuzum's lab developed the implant. They worked with Komiyama's lab to perform brain imaging studies in transgenic mice.

Engineering a multi-use neural probe

What makes this neural implant unique is that it can be used to monitor activity in multiple brain regions at the same time. It can record electrical signals from single neurons deep inside the brain, like in the hippocampus, while imaging large areas like the cerebral cortex.

"Our probe enables us to combine these modalities in the same experiment seamlessly. This cannot be done with current technologies," said Xin Liu, an electrical and computer engineering Ph.D. student in Kuzum's lab. Liu is a co-first author of the study along with Chi Ren, a recent UC San Diego biological sciences Ph.D. graduate who is now a postdoctoral researcher in Komiyama's lab, and Yichen Lu, an electrical and computer engineering Ph.D. student in Kuzum's lab.

Several design features make multi-region monitoring possible. One is that this probe is flexible. When it is inserted deep into the brain to monitor a region like the hippocampus, the part that sticks out of the brain can be bent down and make room for a microscope to be lowered close to the surface to do imaging of the cerebral cortex at the same time. Conventional neural probes are rigid, so they get in the microscope's way; as a result, they cannot be used to monitor deep brain structures while imaging the brain's surface. And even though the UC San Diego team's neural probe is soft and flexible, it is engineered to withstand buckling under pressure during insertion.

Another important feature is that this probe is transparent, so it gives the microscope a clear field of view. It also does not generate any shadows or additional noise during imaging.

Exploring fundamental neuroscience questions

The motivation for this study was getting to the root of how different cognitive processes, such as learning and memory formation, occur in the brain. Such processes involve communication between the hippocampus and cerebral cortex. But how exactly does this communication happen? And which brain region initiates this communication: the hippocampus or the cerebral cortex? These types of questions have been left unanswered because it is very difficult to study these two brain regions simultaneously, said Kuzum.

"We were interested in investigating the nature of cortical-hippocampal interactions, so we built a technology to explore this neuroscience problem," she said.

The researchers used their probe to monitor the activity of the hippocampus and the cerebral cortex in transgenic mice. Specifically, they monitored activity before, during and after oscillations that occur in the hippocampus called sharp-wave ripples.

Their experiments revealed that communication between the hippocampus and cerebral cortex is two-sided: sometimes the cortex initiates communication, other times it's the hippocampus. This is an important first clue for understanding inter-region communication in the brain, the researchers said.

"The hippocampal-cortical interaction is important in memory consolidation and retrieval," said Ren. "The two-sided communication we reported here is different from the conventional notion that the cortex passively receives the information from the hippocampus. Instead, the cortex is actively involved in encoding information into the brain and may play an instructive role during memory consolidation and retrieval."

"We can now begin new studies to unlock how processes like learning and memory happen," said Kuzum. "For example, when the brain acquires new information, how does the hippocampus transfer the memory to the cortex for storage, or does the cortex send a cue to transfer the memory? Our findings show that communication can be initiated by either, but to go beyond that we'd need to do behavioral studies."

This study also reveals that there are diverse and distinct modes of communication between the hippocampus and the cerebral cortex. The researchers found that the hippocampus communicates with at least eight different parts of the cerebral cortex every time sharp-wave ripples occur. Further, each of these eight cortical activity patterns is tied to a different population of neurons in the hippocampus.

"These findings suggest that the interactions between brain regions, not only between cortex and hippocampus, can be fundamentally diverse and flexible. Therefore, multiple brain regions can efficiently work together to generate cognition and behavior that rapidly adapt to changing environments," said Ren.

In the Council of the European Union, member states mostly cooperate with other countries in their geographical proximity. However, once it became clear that the United Kingdom was going to leave the EU, the member states also started cooperating to a greater extent with ideologically like-minded members. Research from the University of Gothenburg shows that Brexit may, in part, have changed the logic behind how cooperation in the Council of the European Union is structured.

The Council of the European Union is one of the most important EU decision-makers. Government ministers from the 27 EU member states participate in the Council meetings to negotiate and make decisions on the European Commission's proposals for EU laws. Which ministers meet depends on the topics to be discussed. It is well-established in the research that member states prefer to cooperate in the Council with their neighbouring countries, which has led researchers to interpret these patterns as relatively stable. However, it is only now that researchers are able to explain what underlies this stability.

Political scientist Markus Johansson has researched the consequences of Brexit on EU cooperation. He studied how the cooperation patterns in the Council of the European Union have changed from the period before the British referendum on Brexit in 2016 compared to the period after.

Given that the cooperation patterns are stable over time, he tested a structural explanation for cooperation which assumes that member states with similar economic and political systems at national level also ought to have more similar interests in EU negotiations. In the study, this is tested against an explanatory model of ideological differences between the governing parties of the member states. This is a more volatile factor as the ideological orientations of governments are affected by national elections and potential changes of government.

"The results indicate that member states with more similar economic and political systems also have stronger partnering relationships and that the effect of this is as significant before as after the Brexit referendum. This provides a first indication that these similarities could be an underlying cause of the stability of partnerships between member states over time, and that they follow geographical patterns."

The ideological differences between the governments were measured on three dimensions: economic left-right, GAL-TAN (green, alternative, libertarian and traditional, authoritarian, nationalist), and attitude to European integration.

"Before the Brexit referendum, none of these ideological dimensions had any effect on relationships between member states. But after the referendum, both the GAL-TAN dimension and attitude to European integration have had an impact on cooperation. Member states that are ideologically similar on these dimensions have cooperated more closely in the period after it became clear that the United Kingdom was going to leave the EU."

The study does not clarify the cause of the change that has taken place. However, it is clear that the remaining member states have had to adapt their relationships to a new political landscape which no longer includes the United Kingdom.

"With the United Kingdom's withdrawal process in progress, EU cooperation has also landed in the political spotlight more generally. This could be a contributor to a more ideological logic behind the new relationships that are established when a member state disappears," says Markus Johansson.

The LUX team at DESY is celebrating not just one but two milestones in the development of innovative plasma accelerators. The scientists from the University of Hamburg and DESY used their accelerator to test a technique that allows the energy distribution of the electron beams produced to be kept particularly narrow. They also used artificial intelligence to allow the accelerator to optimise its own operation. The scientists are reporting their experiments in two papers published shortly after one another in the journal Physical Review Letters. "It's fantastic to see the speed with which the new technology of plasma acceleration is reaching a level of maturity where it can be used in a wide range of applications," congratulates Wim Leemans, Director of the Accelerator Division at DESY.

Plasma acceleration is an innovative technology that is giving rise to a new generation of particle accelerators which are not only remarkably compact but also extremely versatile. The aim is to make the accelerated electrons available for applications in various different fields of industry, science and medicine.

The acceleration takes place in a tiny channel, just a few millimetres long, filled with an ionised gas called a plasma. An intense laser pulse generates a wave within the channel, which can capture and accelerate electrons from the plasma. "Like a surfer, the electrons are carried along by the plasma wave, which accelerates them to high energies," explains Manuel Kirchen, lead author of one of the papers. "Using this technique, plasma accelerators are able to achieve accelerations that are up to a thousand times higher than those of the most powerful machines in use today," adds Sören Jalas, author of the second paper.

However, this compactness is both a curse and a blessing: since the acceleration process is concentrated in a tiny space that is up to 1000 times smaller than conventional, large-scale machines, the acceleration takes place under truly extreme conditions. Therefore, a number of challenges still have to be overcome before the new technology is ready to go into series production.

The research team led by Andreas Maier, an accelerator physicist at DESY, has now reached two critical milestones at the LUX test facility - jointly operated by DESY and the University of Hamburg: they have found a way of significantly reducing the energy distribution of the accelerated electron bunches - one of the most essential properties for many potential applications. To do this, they programmed a self-learning autopilot for the accelerator, which automatically optimises LUX for maximum performance.

The group conducted its experiments using a new type of plasma cell, specially developed for the purpose, whose plasma channel is divided into two regions. The plasma is generated from a mixture of hydrogen and nitrogen in the front part of the cell, which is about 10 millimetres long, while the region behind it is filled with pure hydrogen. As a result, the researchers were able to obtain the electrons for their particle bunch from the front part of the plasma cell, which were then accelerated over the entire rear section of the cell. "Being more tightly bound, the electrons in the nitrogen are released a little later, and that makes them ideal for being accelerated by the plasma wave," explains Manuel Kirchen. The electron bunch also absorbs energy from the plasma wave, changing the shape of the wave. "We were able to take advantage of this effect and adjust the shape of the wave so that the electrons reach the same energy regardless of their position along the wave," adds Kirchen.

Based on this recipe for achieving high electron beam quality, the team then scored a second research success: Sören Jalas and his colleagues were able to use artificial intelligence (IA) to modify an algorithm that controls and optimises the complex system of the plasma accelerator. To do so, the scientists provided the algorithm with a functional model of the plasma accelerator and a set of adjustable parameters, which the algorithm then optimised on its own. Essentially, the system modified five main parameters, including the concentration and density of the gases and the energy and focus of the laser, and used the resulting measurements to search for an operating point at which the electron beam has the optimum quality. "In the course of its balancing act in 5-dimensional space, the algorithm was constantly learning and very quickly refined the model of the accelerator further and further," says Jalas. "The AI takes about an hour to find a stable optimum operating point for the accelerator; by comparison, we estimate that human beings would need over a week."

A further advantage is that all the parameters and measured variables continue to train the accelerator's AI model, making the optimisation process faster, more systematic and more targeted. "The latest progress at LUX means we are well on the way to trying out initial applications for test purposes," explains Andreas Maier, who is in charge of developing lasers for plasma accelerators at DESY. "Ultimately, we also want to use plasma-accelerated electron bunches to operate a free-electron laser."

Helicobacter pylori (H. pylori), a gram-negative pathogen that has infected half of the world's population is a Group I carcinogen according to the WHO. H. pylori resides in the gastric mucosa causing gastritis, ulcers, gastric cancers and malignant lymphoma of the stomach. It can be eradicated in most infected people using a combination of three drugs; antibiotics clarithromycin, amoxicillin, and gastric acid suppressants. Amoxicillin exerts antibacterial activity by inhibiting the biosynthesis of peptidoglycan present in the cell wall of bacteria, and clarithromycin exerts antibacterial activity by inhibiting protein synthesis.

The current success rate of H. pylori eradication is about 90%. Metronidazole is used instead of clarithromycin for secondary eradication, but the eradication success rate is still 75%, and drug-resistant H. pylori is a growing problem. Therefore, it is expected to develop drugs that exhibit anti-H. pylori activity by a mechanism different from those of these antibiotics.

Cholestenone is a cholesterol analog catabolized by intestinal bacteria. In a study led by Dr. Jun Nakayama of the Department of Molecular Pathology, Shinshu University School of Medicine, cholestenone was found to inhibit biosynthesis of the cell wall of the H. pylori, suppressing its growth. The cell wall of H. pylori contains a molecule called cholesteryl α-D-glucopyranoside (CGL). CGL is important for the survival of H. pylori and is biosynthesized from cholesterol around H. pylori. This study showed that the growth of H. pylori was inhibited and its morphology changed from spiral to spherical after 4 days of incubation in the presence of cholestenone. On the other hand, when H. pylori was cultured for 4 days in the presence of cholesterol, β-sitosterol, and cholestanol as sterols with a hydroxyl group at the 3-position, neither growth inhibition nor abnormal morphology of the bacteria was observed (Fig. 1). In addition, CGL biosynthesis was suppressed in H. pylori cultured in the presence of cholestenone, indicating that cholestenone exhibits antibacterial activity by inhibiting CGL biosynthesis. H. pylori growth suppression by cholestenone was also effective against a clinically isolated clarithromycin-resistant H. pylori strain. Furthermore, mice fed a cholestenone-containing diet showed significant eradication of H. pylori in the gastric mucosa. This suggests that cholestenone could be used as an oral medicine to treat H. pylori patients.

Professor Nakayama's research group previously showed that α1,4-linked N-acetylglucosamine contained in gastric gland mucus exhibits anti-H. pylori activity by inhibiting the biosynthesis of CGL, essential for its survival. CGL is biosynthesized by the action of CGL synthase (αCgT) present on the cell wall of H. pylori, in which glucose derived from UDP-glucose binds α1,3 to the hydroxyl group at the 3-position of cholesterol. Cholestenone, on the other hand, is a substance very similar to cholesterol, but with a ketone group at its third position. Therefore, cholestenone cannot be a substrate for CGL synthase, and it is hypothesized that H. pylori cannot biosynthesize CGL in the presence of cholestenone.

Cholestenone is a safe molecule and exhibits antibacterial action by a mechanism of action different from that of conventional antibacterial agents, so it is expected to be a new antibacterial drug against H. pylori including clarithromycin-resistant strain.

Anyone who lives in Okinawa, a subtropical island in Japan, has an appreciation of the intensity of its pig farming industry. The farms have a large effect on the island's economy and culture. According to Japan's Cabinet Office, as of 2018, there were over 225,000 pigs in Okinawa. Pork is a staple in the local diet and is found in many dishes in traditional restaurants. But the presence of the pig farms has another, less welcome, impact - the odor-y kind. Drive through some particularly farm-filled areas with the car's windows wound down and you're sure to be filled with regret.

This smell is, at least in part, caused by a byproduct of the pig farming. Across Okinawa, large amounts of wastewater are produced by the farms. Now, researchers from the Biological Systems Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) have created a new system for treating this wastewater, which they've successfully tested on a local swine farm in Okinawa.

"Our new system uses two different chambers," explained Dr. Anna Prokhorova, lead author of a paper recently published in Bioresource Technology. "In the one chamber, full strength swine wastewater is treated for the removal of odor, pathogens, and organic matter, whereas in the other chamber, excess nitrate and phosphate is removed from wastewater that has already been treated through the traditional aeration system. To the best of our knowledge, this is the first system to successfully treat two different types of wastewater at the same time."

This is a stark contrast to the traditional aeration system currently utilized by farmers which mainly treats organic matter in the wastewater and also converts the ammonium present to nitrate but does not treat the nitrate further. In Japan, the nitrate discharge limit for the livestock industry will soon be lowered to one fifth of the current level (which today sits at 500 milligrams of nitrate-nitrogen per liter) to be in line with other industries. More than 35% of farms in Okinawa are likely to exceed this impending change.

"This is of huge concern because nitrate contamination can have disastrous impacts on both human health and the environment," said Dr Mami Kainuma, group leader in the Biological Systems Unit. "When nitrate is ingested by people, it is converted to nitrite, which impacts the bloods' ability to carry oxygen and can lead to methemoglobinemia or blue baby syndrome."

This new system relied on the existence of a rich community of bacteria to begin the process. In the first chamber - the anode chamber - the bacteria reacted with the organic molecules present, releasing electrons in the process. These electrons were then transferred to the second chamber - the cathode chamber - via the electrodes. The cathode chamber contained wastewater that had already gone through the aeration process and thus had high levels of nitrate. Bacteria on the surface of the cathode chamber accept these electrons and used them to power the conversion of nitrate to nitrogen gas. The advantage of this system is that the nitrate removal can happen in wastewater with low organic matter content, such as the already-aerated water.

After successfully trialing this system in the lab, the researchers set up an initial pilot experiment at one of the pig farms in Okinawa Prefecture Livestock and Grassland Research Center by working with the Okinawa Prefecture Environment Science Center and Okidoyaku. There they had access to both the aeration tank and raw wastewater. The project was funded by Okinawa Prefectural Government and monitored for over a year. Because of the integral role the bacterial communities played, the researchers also analyzed which species were present, how the composition of the community changed over time, and which species were responsible for each step.

The long-term experiment showed that the dominant nitrate-removing bacteria were those that can receive electrons to grow. During the treatment, their activity was stimulated by applied potential to the electrode in a range of -0.4V - -0.6V, which led to more efficient treatment of the wastewater. Such bacterial communities grew by over 60% in total in the cathode chamber, and continued to exhibit strong activity, leading to a high rate of nitrate reduction. Another big advantage was that, as the organic matter and, in particular, the volatile fatty acids were degraded in raw wastewater, the smell was lessened, and the number of pathogens reduced.

"We're very happy with the results so far. It's much more efficient than we expected," said Dr. Prokhorova. "This system is scalable, low cost, easy to assemble, and low maintenance. We're hopeful that, within the next few years, it will be utilized by farmers in Okinawa and other locations with similar issues, such as rural communities in mainland Japan and Southeast Asia."

The work will be continued as a POC program in OIST.

The current loss of biological diversity is unprecedented and species extinctions exceed the estimated background rate many times over. Coinciding with increasing human domination and alteration of the natural world, this loss in abundance and diversity is especially pronounced with - but not limited to - fauna in the tropics. A new publication from scientists at the Lund University Centre for Sustainability Studies (LUCSUS) in Sweden and the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) in Germany now explores the links between defaunation of tropical forests and the United Nations Sustainable Development Goals (SDGs). In a paper published in the scientific journal Ambio they illustrate how losing an abundant and diverse fauna undermines food security, increases the risk of infectious disease outbreaks, reduces the capacity of carbon storage and thereby weakens fundamental pillars of sustainable global development. In the light of these insights, they urge to give defaunation more attention in interdisciplinary research, forest policy and conservation.

Defaunation is a quiet process currently unfolding in tropical forests. It refers not only to the loss of animal species diversity owing to regional or global extinctions, it also includes the circumstance that species are much less abundant and cannot fulfil their ecological roles when they are limited to small numbers. "An empty forest is inherently different from a forest with a healthy animal community. What happens under the canopy of the world's remaining tropical forests is of the utmost importance for achieving the SDGs", say Torsten Krause from LUCSUS and Andrew Tilker from Leibniz-IZW. The scientists explored the links between tropical defaunation and four of the 17 SDGs by reviewing and analysing the available evidence about important social and ecological impacts of defaunation at local and global levels. They show that defaunation threatens critical ecological functions and jeopardises human well-being at different levels.

Nutrition and zero hunger (SDG 2): Wild meat is an important source of nutrition for local people who live within or in close proximity to tropical forests and who depend on it for sustenance. Defaunation increases hunger, reduces access to safe, nutritious and sufficient food throughout the year and enhances malnutrition of children. "It is important to realise that the link also acts as a driver for overexploitation of forest animals", says Tilker. As tropical forest animals play a key role in pollination, a loss of insects, bats or birds can also threaten the yield of non-timber forest products such as fruits or nut-bearing trees - another pillar of food security and health in the tropics.

Good health and well-being (SDG 3): The past 18 months have shown that wild meat consumption can be of global public health importance because wild animals are hosts of and can transmit numerous, potentially fatal zoonotic diseases. "There is mounting evidence that the human-driven loss of tropical forest fauna can significantly increase dispersal of host, parasite and vector species, thus enabling better contact to people and a greater frequency of infectious disease outbreaks", explains Krause. "Leaving faunal communities in tropical forests relatively undisturbed (and in a healthy state) is pivotal to global health." Additionally, a rich and resilient forest fauna is often of great culturally significance and serves as a source of inspiration in art and literature - and contributes to achieving goal 3.4 "to promote mental health and well-being" under SDG 3.

Climate action (SDG 13): Forests are one of the world's most important terrestrial carbon sinks, and maintaining and protecting healthy forest ecosystems is critical to mitigating climate change. Intact faunal communities play a crucial role to maintain such forest ecosystem functions because of the multitude of ecological interactions between plants and animals. "Defaunation changes and loses some of these interactions. Empty forests are much less resilient, for example because they have no seed dispersers", Tilker explains. Recent investigations have demonstrated the direct link of faunal diversity to carbon storage capacity: When large-seeded animal-dispersed trees decline, forests store less carbon. "Defaunation therefore poses an indirect but significant threat to efforts that address climate change."

Life on land (SDG 15): The loss of fauna from the world's tropical forests is directly linked to the ability to protect and sustainably use terrestrial forest ecosystems and their biodiversity in future. Defaunation, therefore, is a direct threat to targets within SDG 15, for example target 15.2 (by 2020, promoting the implementation of sustainable management of all types of forests, halt deforestation, restore degraded forests and substantially increase afforestation and reforestation globally) and target 15.5 (taking urgent and significant action to reduce the degradation of natural habitats, halt the loss of biodiversity and, by 2020, protect and prevent the extinction of threatened species). "In this context, defaunation does not hamper achieving a goal, stopping defaunation is the primary goal and thereby a fundamental pillar of sustainable global development", Krause and Tilker conclude.

In the light of these insights, defaunation needs to be given more attention in various areas of research, environmental governance and conservation at global and local levels. As the consequences of tropical defaunation are far-reaching, but uniquely complex - as the wild meat dilemma illustrates - more interdisciplinary research is needed to fully understand the implications of the process. "The loss of tropical forest fauna has countless ecological, evolutionary, socioeconomic, and cultural repercussions and undermines the achievement of the SDGs, so it is important for scholars studying tropical forest biodiversity to recognize that forests are inherently social-ecological systems", says Tilker. Based on such evidence, holistic and location-based conservation approaches need to be designed in order to mitigate and reverse defaunation. Local socio-economic systems have to play an important role for the success of conservation strategies. Defaunation has also been largely overlooked in forest conservation policies and needs to be directly addressed in forest governance strategies, stimulated for example by including fauna in forest-focused global climate finance. Last but not least, effective action to curb and control the commercial trade of tropical wildlife is a major cornerstone to tackle defaunation of forest ecosystems.