Urban slums are uniquely vulnerable to COVID-19. Here's how to help.

Report provides eight urgent recommendations for reducing the impact of COVID-19 on people living in poverty
UNIVERSITY OF CALIFORNIA - BERKELEY

PEOPLE DWELLING IN URBAN SLUMS ARE UNIQUELY VULNERABLE TO COVID-19, BUT SUFFER UNDER SHELTER-IN-PLACE RESTRICTIONS THAT CAN OFTEN LIMIT THEIR ACCESS TO BASIC NEEDS LIKE FOOD AND WATER.... view more  CREDIT: PHOTO BY JASON CORBURN

Berkeley -- Government-enforced social isolation may help relatively affluent populations limit the spread of COVID-19, but these measures can be devasting for the nearly 1 billion people around the globe currently dwelling in urban slums, where physical space is scarce, and many rely on daily wage labor for survival.

To help the urban poor weather the COVID-19 pandemic, governments should instead prioritize providing basic needs, including fresh water, sanitation and a moratorium on evictions, and support existing community leadership in delivering health care and emergency preparedness, argues a new report published April 24 in the Journal of Urban Health.

The report, authored by a team of public health experts and epidemiologists working in collaboration with community leaders and non-governmental organizations (NGOs) from urban slums around the world, provides eight urgent recommendations for reducing the impact of COVID-19 on people living in poverty.

These recommendations are crucial not just for people living in urban slums in the global south, but for other vulnerable populations, such as migrant farm workers and those living in refugee camps and homeless encampments and on Native American reservations in the United States, the authors say. Evidence now suggests that the coronavirus is disproportionately affecting black Americans in some U.S. cities, possibly due to similar structural factors, such as the inability to take time off of work.

"The political and economic shocks and instability that are happening now and are likely to follow from this epidemic will likely kill more and lead to more disability in this population than the coronavirus itself," said Jason Corburn, a professor of public health and of city and regional planning at the University of California, Berkeley, and lead author of the paper. "We felt we needed a strategy that recognized the unique needs of the urban poor at the front."

Close living conditions and lack of basic sanitation make urban slum dwellers particularly vulnerable to contracting and spreading the coronavirus, said study co-author Lee Riley, a professor of epidemiology and infectious diseases at UC Berkeley. Many also have pre-existing medical conditions and lack access to health care, putting them at high risk of dying or developing serious complications if they do get sick with the virus.

Simply staying home is rarely an option for them, as it often means giving up work and even basic necessities like food, water and sanitation. In some countries, like Kenya and South Africa, people even face government violence for not obeying curfews and other restrictions.

"Shelter-in-place is a luxury of the wealthy," Riley said. "In many slums, people need to walk a long distance to collect water to use at home. Most people living in slums also have no choice but to participate in the informal economy, which will disappear under lockdowns."

Topping the list of recommendations is a call for governments to partner with existing community leadership and NGOs to form emergency planning committees that can consider the unique social, economic and cultural needs of the community in charting the appropriate response, rather than relying on top-down directives.

Similarly, as many communities lack easy access to health care, community and informal health workers should be deployed to monitor individuals for early symptoms and educate them about how to avoid transmitting the disease. Plans should be also be enacted for emergency transport into and out of settlements, which often lack adequate transportation infrastructure.

"The worst thing you can do in an emergency, particularly in an infectious disease outbreak, is to give everybody the same advice, because it doesn't recognize that not everybody starts in the same position," Corburn said. "Community health workers are uniquely positioned to know the preexisting conditions and the constraints that a group faces."

Finally, governments should ensure that people in slums have their basic needs for shelter and food met by enacting a moratorium on evictions and by providing payments for lost work, fresh water and food, and solid waste removal.

"COVID-19 became a pandemic because of the global spread of the virus by those people who can afford to travel on airplanes and cruise ships," Riley said. "As we are now seeing, inevitably, the disease has ended up in vulnerable communities of the world."

"We want to be bold in calling for actions that don't just tinker around the edges," Corburn added. "It's not just about getting people some more care or better care. We're really calling for a more holistic approach to public health."

###

Co-authors of the paper include David Vlahov of the Yale School of Nursing; Blessing Mberu of the African Population and Health Research Center in Kenya; Waleska Teixeira Caiaffa of the Federal University of Minas Gerais School of Medicine in Brazil; Sabina Faiz Rashid of BRAC University in Bangladesh; Albert Ko of the Yale School of Public Health; Sheela Patel and Smurti Jukur of the Society for the Promotion of Area Resource Centers (SPARC) in India; Eliana Martínez-Herrera of the University of Antioquia in Colombia; Saroj Jayasinghe of the University of Colombo in Sri Lanka; Siddharth Agarwal of the Urban Health Resource Centre in India; Blaise Nguendo-Yongsi of the University of Yaoundé II in Cameroon; Jane Weru of the Akiba Mashinani Trust (AMT) in Kenya; Smith Ouma of Cardiff Law and Global Justice at Cardiff University in Kenya; Katia Edmundo of Centro de Promoçâo da Saúde in Brazil; Tolullah Oni of the University of Cape Town, South Africa; and Hany Ayad of Alexandria University in Egypt.

Survey: Most Americans want government commitment to reduce inequality

New national survey shows a majority of Americans want the federal government to reduce inequality amid the Covid-19 economic crisis. Most say the US is increasingly divided between 'haves' and 'have-nots'
LEHIGH UNIVERSITY


A new poll finds that a majority of Americans say that the federal government should commit to reducing economic inequality in this country over the next year, considering the spread of coronavirus in the United States and its impact on the economy and the American people.

A national survey conducted by The Harris Poll on behalf of Lehigh University of 2,018 Americans, conducted between April 7-9, 2020, finds that 78 percent of Americans agree that "considering the spread of coronavirus in the United States and its impact on the economy and the American people," it is "somewhat" or "very important" that "the U.S. government commit to reducing economic inequality" over the next year, through things like "raising the minimum wage" and "taxing households making more than $250,000 a year to guarantee health care coverage to all Americans who lack access." Only 22 percent feel reducing inequality through these actions is "not very important" or "not at all important."

As the polling data show, public attitudes on inequality reduction vary by income, age, and between renters and homeowners. Support for inequality reduction is highest among Americans, age 35-44 (88%, compared to 82% of 18-34, 80% of 45-54 ,74% of 55-64 and 67% of 65+), individuals with household incomes of less than $100,000 a year (81% compared to 73% of those with HHI of $100K+), and renters (84%, compared to 76% of homeowners).

Opinions about the inequality divide are divided. Fifty-seven percent of Americans agree that "in a time of growing economic instability and rising unemployment claims, the U.S. is increasingly divided between the 'haves' and 'have-nots.'" By comparison, 43 percent agree that "recent economic troubles are only temporary, and the economy will soon bounce back, so it makes little sense to speak of 'haves' and 'have-nots.'" Groups that are most likely to agree that the U.S. is divided include younger Americans, aged 18-34 (64%, compared to 54% of 35-54, and 51% of 65+), individuals with household incomes of less than $50,000 a year (61%, compared to 53% of those with HHI of $100k+), and women (60%, compared to 54% of men).

###

Methodology This survey was conducted online within the United States by The Harris Poll on behalf of Lehigh University from April 7 - 9, 2020 among 2,018 U.S. adults ages 18 and older. This online survey is not based on a probability sample and therefore no estimate of theoretical sampling error can be calculated. For complete survey methodology, including weighting variables and subgroup sample sizes, please contact:

Dr. Anthony DiMaggio
Associate Professor, Lehigh University
Department of Political Science
Email: Ard416@lehigh.edu

Experimental Biology press materials available now

Explore exciting research findings published in The FASEB Journal

EXPERIMENTAL BIOLOGY

 

Though the Experimental Biology (EB) 2020 meeting was canceled in response to the COVID-19 outbreak, EB research abstracts are being published in the April 2020 issue of The FASEB Journal.

Explore the journal for the latest findings in anatomy, biochemistry, molecular biology, investigative pathology, pharmacology and physiology. Discover exciting research highlights below and in our Virtual Newsroom.

Vaping

Is It Safe to Vape While Breastfeeding?
Animal study suggests maternal nicotine exposure during breast feeding can affect offspring

Can Vaping Scar Your Lungs? New Insights and a Possible Remedy
E-cigarette liquid found to affect lung tissue repair process; inhibiting nicotine receptors may help

Say No to Vaping: Blood Pressure, Heart Rate Rises in Healthy, Young Nonsmokers

Infectious Disease

"Dirty" Mice Could Help Make a More Effective Flu Vaccine
Study suggests standard laboratory mice may lead scientists to overestimate vaccine efficacy

Scientists Uncover How Zika Virus Can Spread through Sexual Contact
Virus finds hospitable environment in the cells that line the vagina

Treatment Innovations

Light Helps Arthritis Treatments Target Joints
New drug delivery method could reduce side effects from rheumatoid arthritis drugs

Earbud-like Nerve Stimulator Shows Promise for Relieving Indigestion
Non-invasive vagus nerve stimulation helps stomach expand and empty properly

CBD

CBD Shows Promise for Fighting Aggressive Brain Cancer
Study shows that CBD isolate and extract can slow growth and kill cancer cells

What's the Best Way to Identify Male Hemp Seedlings?
More accurate sex determination could increase yields and lower price of CBD

Environment

Tube Worm Slime Displays Long-Lasting, Self-Powered Glow
Marine organism's bioluminescence could inspire new eco-friendly, long-lasting light sources

Scientists Use Bacteria to Help Plants Grow in Salty Soil
Method could be scaled up to help farmers improve crop yield in areas with increased soil salinity

Women's Health

Researchers Identify Drugs that Could Halt Preterm Labor
New approach targets problematic molecular pathway to prevent preterm labor and birth

Breathing During Exercise Is Harder for Women Than Men
With smaller airways, overcoming resistance takes more work

Heart Disease

Scientists Trace Path from PTSD to Heart Disease
Young adults with post-traumatic stress disorder show changes in small blood vessels

Researchers Weave Human Tissue into New Blood Vessels
Versatile tissue engineering approach could aid in repairing damage for many tissues and organs

Blood Test Offers Early Warning of Chemotherapy-Related Heart Problems
Accessible, cost-effective method could help doctors intervene before heart damage occurs

Insights into Why Loud Noise is Bad for Your Health
Mouse studies reveal how noise exposure affects heart health and can lead to cancer-related DNA damage

Brain Health

High-fat Diet Consequences Include Mental Fatigue, Researchers Say
Cognitive abilities were impaired in obese rats

Reducing Early Brain Inflammation Could Slow Alzheimer's Progression
Animal study targets Alzheimer's disease before symptoms are apparent

Less Addictive Form of Buprenorphine May Help Curb Cocaine Relapse
Mouse study shows buprenorphine analog is more effective with reduced potential for abuse

3D Tissue Models Provide Unprecedented Insight into Human Brain Function and Disease
Brain-region specific spheroids can be connected to study complex developmental processes

###

Cancer care model could help us cope with COVID-19, says nanomedicine expert

COVID-19 should be managed more like a chronic disease

UNIVERSITY OF MANCHESTER

As the UK government looks for an exit strategy to Britain's COVID-19 lockdown a nanomedicine expert from The University of Manchester believes a care model usually applied to cancer patients could provide a constructive way forward.

Kostas Kostarelos, is Professor of Nanomedicine at The University of Manchester and is leading the Nanomedicine Lab, which is part of the National Graphene Institute and the Manchester Cancer Research Centre.

The Manchester-based expert believes more scientific research should be employed as we transform how we view the COVID-19 pandemic, or any future virus outbreak, and deal with it more like a chronic disease - an ever present issue for humanity that needs systematic management if we are ever to return to our 'normal' lives.

Professor Kostarelos makes this claim in an academic thesis entitled 'Nanoscale nights of COVID-19' that offers a nanoscience response to the COVID-19 crisis and will be published on Monday, April 27, by the journal Nature Nanotechnology.

"As for any other chronic medical condition, COVID-19 stricken societies have families, jobs, businesses and other commitments. Therefore, our aim is to cure COVID-19 if possible," says Professor Kostarelos.

"However, if no immediate cure is available, such as effective vaccination," Professor Kostarelos suggests: "We need to manage the symptoms to improve the quality of patients' lives by making sure our society can function as near as normal and simultaneously guarantee targeted protection of the ill and most vulnerable."

Professor Kostarelos says his experience in cancer research and nanotechnology suggests a model that could also be applied to a viral pandemic like COVID-19.

"There are three key principles in managing an individual cancer patient: early detection, monitoring and targeting," explains Professor Kostarelos. "These principles, if exercised simultaneously, could provide us with a way forward in the management of COVID-19 and the future pandemics.

"Early detection has improved the prognosis of many cancer patients. Similarly, early detection of individuals and groups, who are infected with COVID-19, could substantially accelerate the ability to manage and treat patients.

"All chronic conditions, such as cancer, are further managed by regular monitoring. Therefore, monitoring should be undertaken not only for patients already infected with COVID-19, to track progression and responses, but also for healthy essential workers to ensure that they remain healthy and to reduce the risk of further spreading.

Finally, says Professor Kostarelos, nanomaterials - as well as other biologicals, such as monoclonal antibodies - are often used for targeting therapeutic agents that will be most effective only against cancer cells.

The same principle of 'targeting' should be applied for the management of COVID-19 patients to be able to safely isolate them and ensure they receive prompt treatment.

Also, a safeguarding strategy should be provided to the most vulnerable segments of the population by, for example, extending social distancing protocols in elderly care homes - but with the provision of emotional and practical support to ensure the wellbeing of this group is fully supported.

"Protection of the most vulnerable and essential workers, must be guaranteed, with protective gear and monitoring continuously provided," he added. "Only if all three principles are applied can the rest of society begin to return to normal function and better support the activities in managing this and all future pandemics."

###

They remember: Communities of microbes found to have working memory

Discovery draws surprising parallels between low-level organisms and sophisticated neurons; lays the groundwork for memory-capable biological systems

UNIVERSITY OF CALIFORNIA - SAN DIEGO


MEMORY IMPRINTS: RESEARCHERS USED LIGHT EXPOSURE TO IMPRESS A COMPLEX PATTERN (UC SAN DIEGO'S FORMER GEISEL LIBRARY LOGO, SPREAD ACROSS AN AREA SLIGHTLY SMALLER THAN THE THICKNESS OF A HUMAN... view more  CREDIT: SUEL LAB, UC SAN DIEGO

Biologists studying collectives of bacteria, or "biofilms," have discovered that these so-called simple organisms feature a robust capacity for memory.

Working in the laboratory of University of California San Diego Professor Gürol Süel, Chih-Yu Yang, Maja Bialecka-Fornal and their colleagues found that bacterial cells stimulated with light remembered the exposure hours after the initial stimulus. The researchers were able to manipulate the process so that memory patterns emerged.

The discovery reveals surprising parallels between low-level single-cell organisms and sophisticated neurons that process memory in the human brain.

"Even just a few years ago people didn't think bacterial cells and neurons were anything alike because they are such different cells," said Süel. "
"This finding in bacteria provides clues and a chance to understand some key features of the brain in a simpler system. If we understand how something as sophisticated as a neuron came to be--its ancient roots--we have a better chance of understanding how and why it works a certain way."

The findings, described April 27 in the journal Cell Systems, also provide a starting path for scientists to one day design basic computing systems with living organisms such as bacteria.

Following recent discoveries by the Süel lab that bacteria use ion channels to communicate with each other, new research suggested that bacteria might also have the ability to store information about their past states. In the new study, the researchers were able to encode complex memory patterns (video here) in bacterial biofilms with light-induced changes in the cell membrane potential of Bacillus subtilis bacteria. The optical imprints, they found, lasted for hours after the initial stimulus, leading to a direct, controllable single-cell resolution depiction of memory.

"When we perturbed these bacteria with light they remembered and responded differently from that point on," said Süel. "So for the first time we can directly visualize which cells have the memory. That's something we can't visualize in the human brain."

The ability to encode memory in bacterial communities, the researchers say, could enable future biological computation through the imprinting of complex spatial memory patterns in biofilms.

"Bacteria are the dominant form of life on this planet," said Süel. "Being able to write memory into a bacterial system and do it in a complex way is one of the first requirements for being able to do computations using bacterial communities."

Further, as the researchers note in the study: "It may thus be possible to imprint synthetic circuits in bacterial biofilms, by activating different kinds of computations in separate areas of the biofilm... Overall, our work is likely to inspire new membrane-potential-based approaches in synthetic biology and provide a bacterial paradigm for memory-capable biological systems."

###

Authors of the study included: Chih-Yu Yang, Maja Bialecka-Fornal, Colleen Weatherwax (graduate student), Joseph Larkin, Arthur Prindle, Jintao Liu, Jordi Garcia-Ojalvo and Gürol Süel.

The study was supported by the National Institute of General Medical Sciences (R01 GM121888), the Howard Hughes Medical Institute-Simons Foundation Faculty Scholars program, the Spanish Ministry of Science, Innovation and Universities and FEDER (PGC2018-101251-B-I00), Maria de Maeztu Programme for Units of Excellence in R\&D (CEX2018-000792-M) and the Generalitat de Catalunya (ICREA Academia programme).


Disclaimer: AAAS and EurekAlert! are not responsible for th

Study analyzes contamination in drug manufacturing plants

Report offers guidelines to help prevent viruses from tainting biopharmaceutical drugs

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

CAMBRIDGE, MA -- Over the past few decades, there have been a handful of incidents in which manufacturing processes for making protein drugs became contaminated with viruses at manufacturing plants. These were all discovered before the drugs reached patients, but many of the incidents led to costly cleanups and in one instance a drug shortage.

A new study from an MIT-led consortium has analyzed 18 of these incidents, most of which had not been publicly reported until now. The report offers insight into the most common sources of viral contamination and makes several recommendations to help companies avoid such incidents in the future.

While the study focused on biopharmaceuticals (protein drugs produced by living cells), the findings could also help biotech companies to create safety guidelines for the manufacture of new gene therapies and cell-based therapies, many of which are now in development and could face similar contamination risks.

"As the biotech industry starts to think about manufacturing these really exciting new products, which are highly effective and even in some cases curative, we want to make sure that the viral safety aspects of manufacturing them are considered," says Stacy Springs, senior director of programs for MIT's Center for Biomedical Innovation (CBI).

Springs is the senior author of the study, which appears today in Nature Biotechnology. Paul Barone, co-director of the CBI's Biomanufacturing Program and director of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB), is the lead author. The other authors from CBI are Michael Wiebe and James Leung.

Sharing information

Many therapeutic proteins are produced using recombinant DNA technology, which allows bacterial, yeast, or mammalian cells to be engineered to produce a desired protein. While this practice has a strong safety record, there is a risk that the cultured mammalian cells can be infected with viruses. The CAACB, which performed the study, was launched in 2010 following a well-publicized contamination incident at a Genzyme manufacturing plant in Boston. The plant had to shut down for about 10 months when some of its production processes became infected with a virus in 2009.

When such incidents occur, drug companies aren't required to make them public unless the incident affects their ability to provide the drug. The CBI team assembled a group of 20 companies that were willing to share information on such incidents, on the condition that the data would be released anonymously.

"We thought it would be very valuable to have industry share their experience of viral contamination, since most companies have had none of these incidents if they're lucky, or maybe one or two at the most," Springs says. "All of that knowledge about how they discovered and managed the event, identified the virus and its source, disinfected and restarted the production facility, and took action to prevent a recurrence was all siloed within individual companies."

The study, which focused on protein drugs produced by mammalian cells, revealed 18 viral contamination incidents since 1985. These occurred at nine of the 20 biopharmaceutical companies that reported data. In 12 of the incidents, the infected cells were Chinese hamster ovary (CHO) cells, which are commonly used to produce protein drugs. The other incidents involved human or nonhuman primate cells.

The viruses that were found in the human and nonhuman primate cells included herpesvirus; human adenovirus, which causes the common cold; and reovirus, which can cause mild gastroenteritis. These viruses may have spread from workers at the plants, the researchers suggest.

In many cases, contamination incidents were first detected because cells were dying or didn't look healthy. In two cases, the cells looked normal but the viral contamination was detected by required safety testing. The most commonly used test takes at least two weeks to yield results, so the contaminating virus can spread further through the manufacturing process before it is detected.

Some companies also use a faster test based on polymerase chain reaction (PCR) technology, but this test has to be customized to look for specific DNA sequences, so it works best when the manufacturers know of specific viruses that are most likely to be found in their manufacturing processes.

New technology

Many of the CAACB member companies are exploring new technologies to inactivate or remove viruses from cell culture media before use, and from products during purification. Additionally, companies are developing rapid virus detection systems that are both sensitive and able to detect a broad spectrum of viruses.

CBI researchers are also working on several technologies that could enable more rapid tests for viral contamination. Much of this research is taking place within a new interdisciplinary research group at the Singapore-MIT Alliance for Science and Technology (SMART), called the Critical Analytics for Manufacturing Personalized Medicines. Led by Krystyn Van Vliet, MIT associate provost and a professor of biological engineering and materials science and engineering, this group, which includes several other MIT faculty members from across departments, is working on about half a dozen technologies to more rapidly detect viruses and other microbes.

"I think that there's a lot of potential for technology development to ameliorate some of the challenges we see," Barone says.

Another strategy that the report recommends, and that some companies are already using, is to reduce or eliminate the use of cell growth medium components that are derived from animal products such as bovine serum. When that isn't possible, another strategy is to perform virus removal or inactivation processes on media before use, which can prevent viruses from entering and contaminating manufacturing processes. Some companies are using a pasteurization-like process called high temperature short time (HTST) treatment, while others use ultraviolet light or nanofiltration.

The researchers hope that their study will also help guide manufacturers of new gene- and cell-therapy products. These therapies, which make use of genes or cells to either replace defective cells or produce a therapeutic molecule within the body, could face similar safety challenges as biopharmaceuticals, the researchers say, as they are often grown in media containing bovine serum or human serum.

"Having done this sharing of information in a systematic way, I think we can accelerate the dissemination of information on best practices, not only within the protein manufacturing industry but also the new industry of cell-based modalities," says James Leung.

###

The research was funded by the members of the CAACB.

THE LITTLE DEATH

Scientists unveil how general anesthesia works

A study in mice and rat brains reveals how general anesthesia dampens high frequency brain activity by weakening synapses

OKINAWA INSTITUTE OF SCIENCE AND TECHNOLOGY (OIST) GRADUATE UNIVERSITY

    SHARE

 PRINT  E-MAIL

IMAGE: THE LARGE SIZE OF THE CALYX OF HELD ALLOWS SCIENTISTS TO VISUALIZE AND MANIPULATE THE SYNAPSE. THE ELECTRODES TOUCHING THE NEURONS CAN BE USED TO EVOKE AND RECORD ELECTRICAL SIGNALS.... view more  CREDIT: OIST

Hailed as one of the most important medical advances, the discovery of general anesthetics - compounds which induce unconsciousness, prevent control of movement and block pain - helped transform dangerous and traumatic operations into safe and routine surgery. But despite their importance, scientists still don't understand exactly how general anesthetics work.

Now, in a study published this week in the Journal of Neuroscience, researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) and Nagoya University have revealed how a commonly used general anesthetic called isoflurane weakens the transmission of electrical signals between neurons, at junctions called synapses.

"Importantly, we found that isoflurane did not block the transmission of all electrical signals equally; the anesthetic had the strongest effect on higher frequency impulses that are required for functions such as cognition or movement, whilst it had minimal effect on low frequency impulses that control life-supporting functions, such as breathing," said Professor Tomoyuki Takahashi, who leads the Cellular and Molecular Synaptic Function (CMSF) Unit at OIST. "This explains how isoflurane is able to cause anesthesia, by preferentially blocking the high frequency signals."

At synapses, signals are sent by presynaptic neurons and received by postsynaptic neurons. At most synapses, communication occurs via chemical messengers - or neurotransmitters.

When an electrical nerve impulse, or action potential, arrives at the end of the presynaptic neuron, this causes synaptic vesicles - tiny membrane 'packets' that contain neurotransmitters - to fuse with the terminal membrane, releasing the neurotransmitters into the gap between neurons. When enough neurotransmitters are sensed by the postsynaptic neuron, this triggers a new action potential in the post-synaptic neuron.

The CMSF unit used rat brain slices to study a giant synapse called the calyx of Held. The scientists induced electrical signals at different frequencies and then detected the action potentials generated in the postsynaptic neuron. They found that as they increased the frequency of electrical signals, isoflurane had a stronger effect on blocking transmission.

To corroborate his unit's findings, Takahashi reached out to Dr. Takayuki Yamashita, a researcher from Nagoya University who conducted experiments on synapses, called cortico-cortical synapses, in the brains of living mice.

Yamashita found that the anesthetic affected cortico-cortical synapses in a similar way to the calyx of Held. When the mice were anesthetized using isoflurane, high frequency transmission was strongly reduced whilst there was less effect on low frequency transmission.

"These experiments both confirmed how isoflurane acts as a general anesthetic," said Takahashi. "But we wanted to understand what underlying mechanisms isoflurane targets to weaken synapses in this frequency-dependent manner."

Tracking down the targets

With further research, the researchers found that isoflurane reduced the amount of neurotransmitter released, by both lowering the probability of the vesicles being released and by reducing the maximum number of vesicles able to be released at a time.

The scientists therefore examined whether isoflurane affected calcium ion channels, which are key in the process of vesicle release. When action potentials arrive at the presynaptic terminal, calcium ion channels in the membrane open, allowing calcium ions to flood in. Synaptic vesicles then detect this rise in calcium, and they fuse with the membrane. The researchers found that isoflurane lowered calcium influx by blocking calcium ion channels, which in turn reduced the probability of vesicle release.

"However, this mechanism alone could not explain how isoflurane reduces the number of releasable vesicles, or the frequency-dependent nature of isoflurane's effect," said Takahashi.

The scientists hypothesized that isoflurane could reduce the number of releasable vesicles by either directly blocking the process of vesicle release by exocytosis, or by indirectly blocking vesicle recycling, where vesicles are reformed by endocytosis and then refilled with neurotransmitter, ready to be released again.

By electrically measuring the changes in the surface area of the presynaptic terminal membrane, which is increased by exocytosis and decreased by endocytosis, the scientists concluded that isoflurane only affected vesicle release by exocytosis, likely by blocking exocytic machinery.

"Crucially, we found that this block only had a major effect on high frequency signals, suggesting that this block on exocytic machinery is the key to isoflurane's anesthetizing effect," said Takahashi.

The scientists proposed that high frequency action potentials trigger such a massive influx of calcium into the presynaptic terminal that isoflurane cannot effectively reduce the calcium concentration. Synaptic strength is therefore weakened predominantly by the direct block of exocytic machinery rather than a reduced probability of vesicle release.

Meanwhile, low frequency impulses trigger less exocytosis, so isoflurane's block on exocytic machinery has little effect. Although isoflurane effectively reduces entry of calcium into the presynaptic terminal, lowering the probability of vesicle release, by itself, is not powerful enough to block postsynaptic action potentials at the calyx of Held and has only a minor effect in cortico-cortical synapses. Low frequency transmission is therefore maintained.

Overall, the series of experiments provide compelling evidence to how isoflurane weakens synapses to induce anesthesia.

"Now that we have established techniques of manipulating and deciphering presynaptic mechanisms, we are ready to apply these techniques to tougher questions, such as presynaptic mechanisms underlying symptoms of neurodegenerative diseases," said Takahashi. "That will be our next challenge."

###

New species of moths discovered in the Alps named after three famous alpinists


PENSOFT PUBLISHERS

A CURVED-HORN MOTH OF THE GENUS CARYOCOLUM FEEDING ON A CARNATION PLANT. THIS GENUS FEEDS EXCLUSIVELY ON PLANTS IN THE CARNATION FAMILY (CARYOPHYLLACEAE). view more  CREDIT: P. BUCHNER / TIROLER LANDESMUSEEN

The discovery of new, still unnamed animal species in a well-researched European region like the Alps is always a small sensation. All the more surprising is the description of a total of three new to science species previously misidentified as long-known alpine moths.

During a genetic project of the Tyrolean State Museums in Innsbruck (Austria), Austrian entomologist and head of the Natural Science Collections Peter Huemer used an integrative research approach that relies on molecular methods to study four European moths. Despite having been known for decades, those species remained quite controversial, because of many unknowns around their biology.

At the end, however, it turned out that the scientist was not dealing with four, but seven species. The three that were not adding up were indeed previously unknown species. Therefore, Huemer described the moths in a paper in the open-access, peer-reviewed journal Alpine Entomology. Curiously, all three species were given the names of legendary alpinists: Reinhold Messner, Peter Habeler and David Lama.

Tribute to three legends in alpinism

"The idea to name the new species in honour of three world-renowned climbers was absolutely no coincidence," explains Huemer.

One of the newly described species, Caryocolum messneri, or Messner's Curved-horn moth, is dedicated to Reinhold Messner. Messner is a famous alpinist who was the first to reach Mount Everest without additional oxygen, but also the first climber to ascend all fourteen peaks over 8,000 metres. For decades, he has been inspiring followers through lectures and books. His is also the Messner Mountain Museum project, which comprises six museums located at six different locations in South Tyrol, northern Italy, where each has the task to educate visitors on "man's encounter with mountains" by showcasing the science of mountains and glaciers, the history of mountaineering and rock climbing, the history of mythical mountains, and the history of mountain-dwelling people.

"So what could have been a better fit for a name for the species that flutters on the doorstep of his residence, the Juval Castle in South Tyrol?" says Huemer.

The second new species, Caryocolum habeleri, or Habeler's Curved-horn moth, honours another extraordinary mountaineer: Peter Habeler. Having joined Messner on his expedition to Mount Everest, he also climbed this mountain without additional oxygen in a first for history. Another achievement is his climbing the famous Eiger North Face in mere 10 hours. Additionally, together with the study's author, he sits on the advisory board of the nature conservation foundation "Blühendes Österreich". However, the species' name is also a nod to Peter Habeler's cousin: Heinz Habeler, recognised as "the master of butterfly and moth research in Styria". His collection is now housed in the Tyrolean State Museums.

The third alpinist, whose name is immortalised in a species name, is David Lama, specially recognised by Huemer for his commitment to conservation. Once, in order to protect endangered butterflies along the steep railway embankments in Innsbruck, Lama took care to secure volunteers in a remarkable action. Nevertheless, Lama earned his fame for his spectacular climbing achievements. His was the first free ascent of the Compressor route on the south-eastern flank of Cerro Torre.

"Unfortunately, David lost his life far too soon in a tragic avalanche accident on 16 April 2019 in Banff National Park, Canada. Now, Caryocolum lamai (Lama's Curved-horn moth) is supposed to make him 'immortal' also in the natural sciences," says Huemer.

Many unresolved questions

The newly described moth species are closely related and belong to the genus Caryocolum of the so-called Curved-horn moths (family Gelechiidae).

As caterpillars, the species of this genus live exclusively on carnation plants. Even though the biology of the new moths is still unknown, because of their collection localities, it could be deduced that plants such as the stone carnation are likely their hosts. All species are restricted to dry and sunny habitats and sometimes inhabit altitudes of up to 2,500 m. So far, they have only been observed with artificial light at night.

While Messner's Curved-horn moth occurs from northern Italy to Greece, the area of ??Habeler´s Curved-horn Moth is limited to the regions between southern France, northern Switzerland and southeastern Germany. On the other hand, Caryocolum lamai, only inhabits a small area in the western Alps of Italy and France.

Research on alpine butterflies and moths has been an important scientific focus at the Tyrolean state museums for decades. In 30 years, Peter Huemer discovered and named over 100 previously unknown to science species of lepidopterans. All these new discoveries have repeatedly shown the gaps in the study of biodiversity, even in Central Europe.

"How could we possibly protect a species that we don't even have a name for is one of the key questions for science that derives from these studies," says Huemer in conclusion.

###

Original source:

Huemer P (2020) Integrative revision of the Caryocolum schleichi species group - a striking example of a temporally changing species concept (Lepidoptera, Gelechiidae). Alpine Entomology 4: 39-63. https://doi.org/10.3897/alpento.4.50703

Origins of humankind
Professor Lee Berger has launched a series of online video lectures that will feature some of our most prized fossil discoveries including Taung Child, Homo naledi and Australopithecus sediba.

Virtual and augmented reality: warnings about the ethical dangers

Limits between reality and virtual experiences
UNIVERSITY OF BARCELONA

RESEARCHERS URGE FOR MORE SCIENTIFIC RESEARCH THAT COULD FORM THE BASIS OF A REGULATORY REGIME SUCH AS THERE IS FOR CINEMA. view more CREDIT: UNIVERSITY OF BARCELONA

Research on virtual reality started in the eighties, but it is now that good quality is available to the public and it can become a mass consumer product soon. However, there is almost no scientific knowledge on the effects of virtual reality in the long run, nor any oversight over content.

An international group of researchers, with the participation of Mel Slater, director of Event Lab in the Faculty of Psychology of the University of Barcelona (UB), has published a new paper in the journal Frontiers in Virtual Reality reflecting on potential ethical problems of mass spread of virtual and augmented reality. Researchers warn about the dangers that might arise as these technologies becomes more and more realistic and urge for new research to address these scenarios.

Other participants in the study are representatives of major companies and institutions such as BBC R&D, Digital Catapult, Dimension /Hammerhead VR, Facebook London, NESTA, Jigsaw -part of Google-, Magic Leap, Microsoft Research, and University College London.

Potential negative effects of virtual or augmented reality have not been explored

Virtual reality started more than forty years ago in a form we would recognize today: a stereo head-mounted display, head tracking, and computer graphics generated images. Despite different ups and downs in the development of the technology, a huge amount of research has been carried out across a vast range of applications in the last twenty-five years: from medicine to business, from psychotherapy to industry, from sports to travel.

However, its possible negative effects have not been explored, especially when very high quality visual and behavioral realism of virtual humans is becoming increasingly likely in the near future. Elements and even experiences in virtual or augmented reality may become indistinguishable from reality very soon. "For example, a normal computer game may be violent, but it is violence depicted through a screen, involving tiny characters. In VR you are part of the scenario, everything happening is around you, the characters are life-sized, they can look you in the eye. This is a qualitatively different type of experience compared to video games or movies," said Mel Slater, also a member of the Institute of Neurosciences of the UB (UBNeuro).

"Virtual Reality has been used almost exclusively for the good, mostly focused on psychotherapy, but - continues Mel Slater - like any technology, it can be used for good or evil. In order to prevent its use for evil we need better scientific understanding, and therefore research into its effects."

Limits between reality and virtual experiences

In order to reflect about potential dangers of virtual and augmented reality the working group set out to consider possible worst-case scenarios and possible areas of research to address these. They concentrated mainly on problems that might arise as XR becomes more and more realistic. As virtual reality becomes more real people may find it difficult to distinguish between reality and virtual reality. For example, remembering virtual events as if they had been real, and failing to distinguish over time events that really happened and those that happened in virtual reality.

Researchers also highlighted another potential problem with an ultrarealistic experience: we don't know what are the after effects and mental consequences of using virtual reality - for example in extreme violent games - and of the real-world transition from virtual reality.

"After an intense and emotional experience in virtual reality, you take the headset off, and you are suddenly in the very different real world. We are not good at rapid adjustment of behavior and emotion regulation. Re-entry to the real world, especially after repeated exposure to virtual reality, might lead to disturbances of various types: cognitive (did something happen in XR or in real life?), emotional (cause of emotions is not real, for example your avatar was insulted by a fictional virtual character), and behavioral: for example, actions accepted in XR may not be socially accepted in the real world)," explained Mel Slater.

Social isolation is other issue highlighted in the paper. "It is possible that some people may use XR to such an extent that they lose social face-to-face contact with other people so that people withdraw from society," said Mel Slater.

Some other issues they warn against were data privacy and the dangers of identity impersonation and fake news. "People (e.g., politicians) could be shown to carry out actions in virtual reality that they never did in reality. Although the same is true with just video, in virtual reality it is more powerful because it seems to happen life-sized in the same space in which you are located. It happens in front of you, not through a screen," said Slater.

A regulatory regime similar to cinema
Given these ethical challenges, researchers highlighted that there is essentially no data that can help in addressing them. So, besides the potential problems, some important research questions are outlined in the paper, such as the long-term effects of XR use, or whether XR experiences can be used to manipulate memory, or if people will continue to distinguish real from virtual events.

"It is especially important to make the creators of virtual and augmented reality applications aware of these possible dangers. However, this must be based on scientific study rather than opinion, so an urgent consideration is the funding of interdisciplinary research to address these and other issues. The most important is scientific research that could form the basis of a regulatory regime such as there is for cinema, with classifications of content by age and other conditions," said Mel Slater.

A permanent working group

After this research paper, the working group will continue with regularly meetings and discussion. "We plan to hold a one-day Workshop for Industry where we present these issues in a public forum, and form a more permanent working group from this to advise industry, government and international bodies," said Mel Salter.

###