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."

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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).


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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.

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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

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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."

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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.

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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.

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University of the Witwatersrand publishes first clinical data on COVID-19 in South Africa

This special issue of the Wits Journal of Clinical Medicine covers a range of aspects of the pandemic, from the clinical, through ethical, to the social dynamics of its impact

UNIVERSITY OF THE WITWATERSRAND

THE JOURNAL, PUBLISHED BY WITS UNIVERSITY PRESS UNDER OPEN ACCESS CONDITIONS, PRESENTS THE FIRST CLINICAL DATA ON COVID-19 PUBLISHED IN SOUTH AFRICA. CREDIT: WITS UNIVERSITY
http://www.wits.ac.za/covid19/covid19-news/latest/wits-publishes-first-clinical-data-on-covid-19-in-south-africa.html

For example, do they resuscitate patients even though the prospects of recovery are slim and the risk to the healthcare team high? How should healthcare workers respond?

This is one of the topics covered in the COVID-19 Special Issue of the Wits Journal of Clinical Medicine. The journal, published by Wits University Press under open access conditions, presents the first clinical data on COVID-19 published in South Africa.

The special issue covers a range of aspects of the pandemic, from the clinical, through ethical, to the social dynamics of its impact.

Highlights include:

Diagnosis of COVID-19: Considerations, controversies and challenges in South Africa
Social dimensions of COVID-19 in South Africa: A neglected element of the treatment plan
Clinical ethical challenges in the COVID-19 crisis in South Africa
Potential impact of SARS-CoV-2 infection in HIV-positive patients in South Africa
COVID-19: The concept of herd immunity - is it a strategy for South Africa?

Editor-in-chief of the Wits Journal of Clinical Medicine Professor Pravin Manga says it is important for health professionals and the public to have access to scientific information:

"Social media is awash with all sorts of quackery regarding prevention and treatment remedies for COVID-19 and it is during these times that we need to be rational and be guided by science rather than by emotion."

Manga is Professor of Internal Medicine, School of Clinical Medicine, in the Faculty of Health Sciences at Wits.

In addition to being a public resource, more than 10 articles in this issue aim to guide healthcare workers. These articles address the ethical aspects related to the pandemic.

For example, which patients should healthcare workers admit to already-filled intensive care units and who decides this? Associate Professor Kevin Behrens, Director and Head of the Steve Biko Centre for Bioethics discusses such ethical conundrums in his review.

Professor Laurel Baldwin-Ragaven in the Department of Family Medicine and Primary Care presents a sobering overview of how some of South Africa's vast social disparities may manifest during COVID-19, and outlines our clinical and social responsibilities.

Professor Charles Feldman in the Division of Pulmonology, Department of Internal Medicine at Wits interrogates the aggravating issue of South Africa's additional burdens of HIV and tuberculosis and the risk of COVID-19 infection in HIV-positive patients.

Professor Ismail S. Kalla in Pulmonology in Internal Medicine and Professor Abdullah Laher in Emergency Medicine in the School of Clinical Medicine explore whether herd immunity offers possibilities as a strategy for fighting COVID-19 in South Africa.

This special issue includes a guide to worldwide Medical Resources on COVID-19, as well as a handy poster-style patient guide for healthcare workers.

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*Covid-19 Resources for Academics and Students: Access the entire Wits University Press eBook collection in your university library through JSTOR and Proquest until 1 July 2020.

How do epidemics spread and persist before and after introduction of a vaccine?

Modeling 40 years of measles dynamics demonstrates the complexity of epidemic spread and the impact of vaccination

PENN STATE

CAPTION

Illustration of the observed measles epidemics in cities and towns of Enland and Wales from 1944-94 (vertical Z-axis represents the timeline) for the largest locations. New research reveals that, prior to the introduction of the measles vaccine, transmission patterns were likely driven by periodic epidemics from both large population centers CREDIT: MAX S. Y. LAU

In the most detailed study to date of epidemic spread, an international team of researchers has modeled measles dynamics based on over 40 years of data collected in England and Wales. The models--which span the prevaccination period, introduction of measles vaccination, and local elimination by vaccination in the 1990s--reveal that, before the introduction of a vaccine, measles could persist in both large population centers and by spread among sets of smaller towns. The study also provides critical data on the importance of spatial modeling for the long-term control of global epidemics and could help inform the long-term public health response to the current COVID-19 pandemic.

A paper describing the study appears April 27, 2020 in the journal Nature Ecology & Evolution.

"During the last 20 years there have been tremendous inroads towards eradicating measles--one of the major killers of children globally--as annual deaths have been driven down from more than a million to less than 200,000," said Ottar N. Bjørnstad, Distinguished Professor of Entomology and Biology at Penn State and one of the leaders of the research team. "However, previous efforts to eradicate smallpox and polio highlight the complexity of moving from local control to global eradication. Our study provides critical data on how long-term control efforts will need both general and detailed spatial models to finally stop this deadly disease."

Prior to the introduction of a vaccine, the number of measles cases in England and Wales would undergo, periodic--often biennial--epidemics. This pattern, driven by herd immunity, is common among a number of diseases and in other locales. The researchers sought to locate the reservoirs where the virus persists in the dips between epidemics, which are the sources for reintroduction of the virus into the general populace in the next major epidemic. This persistence question is central to understanding the dynamics of measles and other viral diseases and for coordinating public health interventions.

The research team combined spatial modeling with the detailed historical data of measles cases in England and Wales to address these questions. The uniquely detailed dataset includes weekly measles reports from almost a thousand locations across England and Wales beginning in 1944 and continuing until the disease was all but locally eliminated by vaccination in the 1990s.

"Previous work stressed the importance of large centers as sources of infection," said Bryan T. Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and of Public Affairs at Princeton University and another leader of the research team. "However, our new modeling shows that local spread among smaller towns can also contribute to persistence of the virus."

The researchers' new model quantifies the relative influence of different sources of infection, including major cities, spread among smaller towns, and unidentifiable outside sources. Following the introduction of vaccination, the source of reintroduction shifted from a combination of large centers and local spread to mainly unidentifiable sources, possibly outside of England and Wales.

"Having access to this unique dataset allowed us to test these news models of measles dynamics with unprecedented rigor," said Max S. Y. Lau, assistant professor in the Rollins School of Public Health at Emory University and first author of the paper. "Going forward, we can apply what we learn from this test case to understand disease spread beyond measles."

"Measles has always been the 'model organism' of epidemic dynamics--like C. elegans or the fruitfly are for evolution--and, along with influenza, a paradigm for understanding herd immunity," said Grenfell. "So, as COVID-19 approaches endemicity, these new models can help us understand and prepare for modeling its spatial spread, as well as understand the impact that the eventual development of a vaccine might have on its dynamics."

Beyond the COVID-19 pandemic, the models also could help scientists understand how diseases survive and spread at a time when a portion of the public is opposed to vaccines, said co-author C. Jessica E. Metcalf, assistant professor of ecology and evolutionary biology and public affairs. "Understanding the drivers of persistence is also of growing importance in a context of growing vaccine hesitancy, which further complicates dynamics and amplifies the challenges of control," she said.

The researchers added that wide perspective should be taken when applying the results to other diseases.

"Our model and previous experience highlights the complexity of globally eradicating a virus," said Bjørnstad. "Smallpox was eradicated by 1977 through a massive global effort of mass-vaccination of all children, followed by targeted efforts in regional hotspots and finally local quarantining and ring vaccination to squash the scourge. Polio, in contrast, while also targeted through vaccination for more than 50 years keeps escaping 'the final blow' as it successfully shifts and diffuses across regional pockets of susceptible individuals to evade eradication."

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In addition to Bjørnstad, Grenfell, Lau, and Metcalf, the research team included, from Princeton, Ph.D. candidates Alexander Becker in ecology and evolutionary biology and Hannah M. Korevaar in the Office of Population Research, and postdoctoral researcher Quentin Caudron; and Darren J. Shaw at the University of Edinburgh.

The research was supported by the RAPIDD Program of the US Department of Homeland Security and the Fogarty International Centre, the US National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the US National Science Foundation.

Disappearance of animal species takes mental, cultural and material toll on humans

Hunter-gatherer societies have had profoundly deep relationships with the animals they hunted, Tel Aviv University researchers say

AMERICAN FRIENDS OF TEL AVIV UNIVERSITYFor thousands of years, indigenous hunting societies have subsisted on specific animals for their survival. How have these hunter-gatherers been affected when these animals migrate or go extinct?

To answer this and other questions, Tel Aviv University (TAU) researchers conducted a broad survey of several hunter-gatherer societies across history in a retrospective study published on January 30 in Time and Mind. The study, led by Eyal Halfon and Prof. Ran Barkai of TAU's Department of Archeology and Ancient Near Eastern Cultures, sheds new light on the deep, multidimensional connection between humans and animals.

"There has been much discussion of the impact of people on the disappearance of animal species, mostly through hunting," explains Halfon. "But we flipped the issue to discover how the disappearance of animals -- either through extinction or migration -- has affected people."

The research reveals that these societies expressed a deep emotional and psychological connection with the animal species they hunted, especially after their disappearance. The study will help anthropologists and others understand the profound environmental changes taking place in our own lifetimes.

Halfon and Prof. Barkai conducted a survey of different historical periods and geographical locations, focusing on hunter-gatherer societies that hunted animals as the basis for their subsistence. They also investigated situations in which these animals became extinct or moved to more hospitable regions as a result of climate change.

"We found that humans reacted to the loss of the animal they hunted -- a significant partner in deep, varied and fundamental ways," Halfon says.

The new research explores hunter-gatherer societies throughout human history, from those dating back hundreds of thousands of years to modern-day societies that still function much the way prehistoric groups did. Ten case studies illustrate the deep connection -- existential, physical, spiritual and emotional -- between humans and animals they hunted.

"Many hunter-gatherer populations were based on one type of animal that provided many necessities such as food, clothing, tools and fuel," Prof. Barkai says. "For example, until 400,000 years ago prehistoric humans in Israel hunted elephants. Up to 40,000 years ago, residents of Northern Siberia hunted the woolly mammoth. When these animals disappeared from those areas, this had major ramifications for humans, who needed to respond and adapt to a new situation. Some had to completely change their way of life to survive."

 According to the study, human groups adapted in different ways. Siberian residents seeking sustenance after the disappearance of mammoths migrated east and became the first settlers of Alaska and northern Canada. Cave dwellers in central Israel's Qesem Cave (excavated by Prof. Barkai) hunted fallow deer, far smaller than elephants, which required agility and social connections instead of robust physical strength. This necessitated far-reaching changes in their material and social culture and, subsequently, physical structure.

Halfon stresses the emotional reaction to an animal group's disappearance. "Humans felt deeply connected to the animals they hunted, considering them partners in nature, and appreciating them for the livelihood and sustenance they provided," he says. "We believe they never forgot these animals -- even long after they disappeared from the landscape."

An intriguing example of this kind of memory can be found in engravings from the Late Paleolithic period in Europe, which feature animals like mammoths and seals. Studies show that most of these depictions were created long after these two animals disappeared from the vicinity.

"These depictions reflect a simple human emotion we all know very well: longing," says Halfon. "Early humans remembered the animals that disappeared and perpetuated them, just like a poet who writes a song about his beloved who left him."

According to Prof. Barkai, another emotional response was a sense of responsibility -- even guilt. "Indigenous hunter-gatherer societies have been very careful to maintain clear rules about hunting. As a result, when an animal disappears, they ask: 'Did we behave properly? Is it angry and punishing us? What can we do to convince it to come back?'" he concludes. "Such a reaction has been exhibited by modern-day hunter-gatherer societies as well."

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American Friends of Tel Aviv University supports Israel's most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. TAU is ranked ninth in the world, and first in Israel, for producing start-up founders of billion-dollar companies, an achievement that surpassed several Ivy League universities. To date, 2,500 US patents have been filed by Tel Aviv University researchers -- ranking TAU #1 in Israel, #10 outside of the US and #66 in the world.

A new explanation for the origins of human fatherhood

Dads emerged to reap the benefits of partnerships with females and other males, team of anthropologists and economists argue

BOSTON COLLEGEChestnut Hill, Mass. (4/27/2020) - Humans differ from other primates in the types and amounts of care that males provide for their offspring. The precise timing of the emergence of human "fatherhood" is unknown, but a new theory proposes that it emerged from a need for partnership in response to changing ecological conditions, U.S. and French researchers report today in the Proceedings of the National Academy of Sciences.

The new theory was developed using tools of economists and knowledge of the economic and reproductive behavior of human foragers. The theory focuses on the benefits of a "fit" between exclusive partners that enabled the strengths of males and females to provide for one another and their offspring, according to researchers from Boston College, Chapman University, University of New Mexico, and the University of Toulouse in France.

Scientists have long tried to explain how human fatherhood emerged. Paternal care - those investments in offspring made by a biological father - is rare among mammals but widespread across modern human subsistence societies. Much of men's parental investment consists of provisioning relatively helpless children with food for prolonged periods of time - for as long as two decades among modern hunter-gatherers. This is a sharp break with other great apes, whose observed mating systems do not encourage paternal provisioning.

That paternal provisioning arose in humans seems remarkable and puzzling and has revolved around a discussion about two groups of males dubbed "Dads" and "Cads".

With promiscuous mating, a would-be Dad who provides food for a mate and their joint offspring without seeking additional mates risks being outcompeted in terms of biological fitness by a Cad, who focuses only on promiscuous mating instead of investing in offspring. Such a competitive disadvantage creates a formidable barrier for Dads to emerge when Cads abound.

An oft-invoked explanation for the evolution of paternal provisioning in humans is that ancestral females started mating preferentially with males who provided them with food, in exchange for female sexual fidelity. This explanation is insufficient for several reasons, the researchers write.

Instead, the team of anthropologists and economists argues that ecological change would have sufficed to trigger the spread of Dads, even in the face of female sexual infidelity, according to the report, "Paternal provisioning results from ecological change."

The key force in the theory of paternal provisioning is complementarities - in essence the cooperation between females and males, as well as between males. Complementarities are synergistic effects that increase per-capita benefits, which may arise from dividing labor and/or pooling resources. The path to complementarities began roughly five to eight million years ago, with a gradual drying in Africa, and a progressively greater need to rely on nutritious, diverse, spatially dispersed and relatively hard-to-obtain foods, including animal products.

In response to ecological change, ancestral hominins adapted in various ways, including efficient bipedal locomotion, dietary flexibility, and an ability to thrive in diverse environments, facilitated by tool use. Complementarities between males and females would have resulted from the nutrients that each sex specialized in acquiring: protein and fat acquired by males paired well with carbohydrates acquired by females.

Complementarities between males would have resulted from higher returns from hunting in groups instead of in isolation, and from food sharing to lower starvation risk. Dietary reliance on animal products is thus a key feature underlying these complementarities between and within sexes.

These complementarities would have led to a substantial increase in the impact of food provided by a Dad on the survival of his mate's offspring.

Using evolutionary game theory, the authors show that this impact can lead Dads to gain a fitness advantage over Cads, although Cads may still co-exist with Dads under certain conditions. If sons inherit their biological father's traits, then over time Dads will increase in number in a population. Theoretically connecting the evolution of paternal provisioning to ecological change allows the authors to make novel predictions about the paleontological and archeological record.

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