Friday, April 3, 2020

Is COVID-19 in the Water System? It's Infectious for Days in Sewage and Drinking Water


Scientists call for more research to understand whether water treatment methods kill the virus responsible for the COVID-19 pandemic.

Scientists know that coronaviruses, including the SARS-CoV-19 virus responsible for the COVID-19 pandemic, can remain infectious for days -- or even longer -- in sewage and drinking water. 

running tap water
Credit: University of California, Riverside

Two researchers, Haizhou Liu, an associate professor of chemical and environmental engineering at the University of California, Riverside; and Professor Vincenzo Naddeo, director of the Sanitary Environmental Engineering Division at the University of Salerno, have called for more testing to determine whether water treatment methods are effective in killing SARS-CoV-19 and coronaviruses in general.

The virus can be transported in microscopic water droplets, or aerosols, which enter the air through evaporation or spray, the researchers wrote in an editorial for Environmental Science: Water Research & Technology, a leading environmental journal of the Royal Society of Chemistry in the United Kingdom.

"The ongoing COVID-19 pandemic highlights the urgent need for a careful evaluation of the fate and control of this contagious virus in the environment," Liu said. "Environmental engineers like us are well positioned to apply our expertise to address these needs with international collaborations to protect public health."

During a 2003 SARS outbreak in Hong Kong, a sewage leak caused a cluster of cases through aerosolization. Though no known cases of COVID-19 have been caused by sewage leaks, the novel coronavirus is closely related to the one that causes SARS, and infection via this route could be possible.

The novel coronavirus could also colonize biofilms that line drinking water systems, making showerheads a possible source of aerosolized transmission. This transmission pathway is thought to be a major source of exposure to the bacteria that causes Legionnaire's disease, for example.

Fortunately, most water treatment routines are thought to kill or remove coronaviruses effectively in both drinking and wastewater. Oxidation with hypochlorous acid or peracetic acid, and inactivation by ultraviolet irradiation, as well as chlorine, are thought to kill coronaviruses. In wastewater treatment plants that use membrane bioreactors, the synergistic effects of beneficial microorganisms and the physical separation of suspended solids filter out viruses concentrated in the sewage sludge.

Liu and Naddeo caution, however, that most of these methods have not been studied for effectiveness specifically on SARS-CoV-19 and other coronaviruses, and they have called for additional research.

They also suggest upgrading existing water and wastewater treatment infrastructure in outbreak hot spots, which possibly receive coronavirus from places such as hospitals, community clinics, and nursing homes. For example, energy-efficient, light-emitting, diode-based, ultraviolet point-of-use systems could disinfect water before it enters the public treatment system.

Potable water-reuse systems, which purify wastewater back into tap water, also need thorough investigation for coronavirus removal, and possibly new regulatory standards for disinfection, the researchers wrote.

The extent to which viruses can colonize biofilms is also not yet known. Biofilms are thin, slimy bacterial growths that line the pipes of many aging drinking water systems. Better monitoring of coronaviruses in biofilms might be necessary to prevent outbreaks.

The surge in household use of bactericides, virucides and disinfectants will probably cause an increase of antibiotic-resistant bacteria in the environment. Treated wastewater discharged into natural waterways demands careful monitoring through the entire water cycle. Liu and Naddeo call on chemists, environmental engineers, microbiologists, and public health specialists to develop multidisciplinary and practical solutions for safe drinking water and healthy aquatic environments.

Lastly, developing countries and some regions within highly developed nations, such as rural and impoverished communities, which lack the basic infrastructure to remove other common contaminants might not be able to remove SARS-CoV-19 either. These places might experience frequent COVID-19 outbreaks that spread easily through globalized trade and travel. Liu and Naddeo suggest governments of developed countries must support and finance water and sanitation systems wherever they are needed.

"It is now clear to all that globalization also introduces new health risks. Where water and sanitation systems are not adequate, the risk of finding novel viruses is very high," Naddeo said. "In a responsible and ideal scenario, the governments of developed countries must support and finance water and sanitation systems in developing countries, in order to also protect the citizens of their own countries."



Contacts and sources: 
Holly Ober
University of California, Riverside


Publication:   





The Anti-Oxidant Differences Between Cold- And Hot-Brew Coffee



Cold brew may be the hottest trend in coffee-making, but not a lot is known about how this process alters the drink’s chemical characteristics. Scientists now report that the content of potentially health-promoting antioxidants in coffee brewed without heat can significantly differ from a cup of joe prepared with the same beans in the traditional way, particularly for dark roasts.

Cold-brew coffee’s antioxidant profile differs from that of hot joe.
Photo Credit: New Africa/Shutterstock.com


The researchers are presenting their results through the American Chemical Society (ACS) SciMeetings online platform.

A brand-new video on the research is available 
Credit: American Chemical Society  .

“This study can inform coffee enthusiasts about how they may want to craft their own coffee at home, based on science and on analytical chemistry,” says Meghan Grim, an undergraduate student who worked on the project.

“After I first tried cold-brew coffee, I wanted to make it at home, but it didn’t turn out too great,” says Niny Z. Rao, Ph.D., the project’s principal investigator. With her collaborator, Megan Fuller, Ph.D., Rao looked into the scientific literature to learn what she had done wrong. “It turns out there weren’t any studies on cold-brew coffee at the time,” Rao says, “so we decided to do some.”

In the cold-brew process, ground coffee is mixed with room-temperature or colder water and steeped for as long as two days, sometimes in a refrigerator. It can be drunk cold or hot. In hot brewing, ground coffee is mixed with boiling or near-boiling water and steeped at most for a few minutes. In either case, the coffee grounds are sometimes pressed, and the beverage is then filtered to remove the grounds.

The researchers, who are at Thomas Jefferson University, previously assessed acidity and antioxidants in hot- and cold-brew java from lightly roasted beans. In another project, they analyzed the effect of medium and dark roasting, and of medium and coarse grinding, on a few coffee attributes. Now they’re taking a deeper dive by roasting Columbian beans at five different temperatures — from light roasting at 174 C to dark roasting at 209 C — and studying the impact on acidity, antioxidants and other natural chemicals in hot- and cold-brew coffee.

With the lighter roasts, Rao’s team finds that the content of caffeine and antioxidants is pretty similar in hot and cold brews. However, significant differences show up with the darker roasts. “Hot brewing extracts more antioxidants from the grind than cold brew, and this difference increases with the degree of roasting,” Rao says. So hot-brew of dark roasts produces a potentially healthier drink. Hot brew also contains more of certain kinds of acids and total dissolved solids. The pH is about the same for both hot and cold brews at equivalent roast, though both become less acidic as roasting temperature increases.

“My advice to consumers has always been to drink what they like,” Rao says. “But if you want to craft a coffee beverage with antioxidants or acidity in mind, you may want to pay attention to roast. If you want a low-acid drink, you may want to use a darker roast. But remember that the gap between the antioxidant content of hot- and cold-brew coffee is much larger for a darker roast.”

One of the biggest challenges in all these projects is reproducibility. “We have performed experiments in which we’re using the same beans, the same machine, the same settings, and it comes out not quite the same as the previous batch,” Rao says. “The same goes for brewing. To create a cup that’s consistent every time is really difficult. I have a lot of respect for the baristas who can do that.” To approach that level of perfection, the researchers became like drill sergeants, carefully standardizing their processes. They developed a procedure for when the water should be added to the ground coffee, how to pour the water and for how long, how to shake the solution, how to press the brewed coffee and how to analyze it. They set time limits for each step, with margins of just a few seconds. This rigor produced much more reproducible results.

The team has now begun comparing the impact of the two brewing processes and degree of roast on furans, flavor compounds present in raw coffee beans that are also generated through roasting. Such compounds are particularly important in cold-brew joe, which doesn’t have the same distinct aroma as the hot drink because it lacks steam to carry volatile organic compounds to the nose.

The researchers acknowledge support and funding from the U.S. Department of Agriculture’s National Institute of Food and Agriculture.


Contacts and sources: 
American Chemical Society






Lifestyle Changes Could Delay Memory Problems In Old Age, Depending On Our Genes



Researchers from King’s College London have shown that how we respond to changes in nutrients at a molecular level plays an important role in the ageing process, and this is directed by some key genetic mechanisms.
Credit: King’s College London

Published in Communications Biology, the study explored the molecular interactions that occur in our response to varying levels of nutrients, otherwise known as nutrient-sensing pathways, as we grow older.

Using a combination of laboratory-based techniques and analysis of data on people’s memory, diet and level of physical exercise, researchers identified a number of genes that are active in nutrient-sensing pathways and demonstrated these genes also show associations to performance on memory tasks in data from over 2000 individuals. The study identified that the genes ABTB1 and GRB10 were both influential in nutrient sensing pathways and showed association to memory.

Advances in medicine and healthcare over the past century have led to increased life expectancies. However, ageing is still accompanied by frailty and a decline in our thought processes. This level of decline varies enormously across individuals and an improved understanding of what influences these ageing mechanisms could help develop strategies to increase “healthspan”, which is the period of time free from debilitating disease.

Previous studies have indicated that neural stem cells (NSCs) in the hippocampal part of the brain play an important role in the decline of our thought processes and memory over time. NSCs are cells that keep dividing as long as they are alive and either make more NSCs or cells that have a specialist function in the brain. The maintenance of these NSCs is important in memory and is affected by environmental factors such as diet and exercise, potentially explaining some of the variation in how ageing affects different people.

Although the role of nutrient-sensing-pathways in ageing and the maintenance of stem cells in the brain has been investigated in animal models, no human studies have so far investigated their role in NSCs in the hippocampus.

Graphical summary of the cellular and epidemiological experiments

Credit: King’s College London

The study aimed to explore whether nutrient-sensing pathways can provide the molecular basis for the association between lifestyle and ageing. These pathways have been implicated in stem cell maintenance, suggesting they could also be involved in the interaction between lifestyle, NSCs and cognition.

Using a novel back-translation approach which uses laboratory-based experiments on NSCs to inform analysis of epidemiological data, rather than vice versa, the researchers showed that variations in ABTB1 are associated to performance on a standard memory task and that variation in the gene GRB10 is an important player in determining the association between Mediterranean diet and memory performance. The study also identified an interaction between exercise levels and the SIRT1 genotype which appears to play a role in memory performance.

Our study shows that nutrient-sensing pathways play an important role in memory and suggests that the ABTB1 and GRB10 genes are likely molecular links for the association between diet, the ageing of neural stem cells and our memory ability. Identifying these genes as the missing links between these three important variables could inform new approaches to help improve the ageing process through targeted changes in diet and exercise and ultimately in developing new drugs in the future.– Lead author, Chiara de Lucia, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London


Senior author, Dr Sandrine Thuret from the IoPPN said: ‘Finding the means to prevent or slow down the processes that drive the decline of our thought processes during ageing is one of the great endeavours of the 21st century. To our knowledge this is one of the first studies looking at these relationships with human data and adopting this back-translation approach which uses lab-based experiments to inform research on large datasets, allowing for a more targeted approach.’

‘Our findings suggest that changes in lifestyle may be able to delay a decline in memory and thinking but that the effectiveness of these approaches will depend on the genetic makeup of each person. For example, adherence to a diet such as the Mediterranean diet may be most beneficial for people with a specific GRB10 mutation while increased exercise may be a better approach for participants with specific SIRT1 variations.’

Future research should look to replicate these findings on a larger dataset which would allow for the testing of three-way interactions between diet, exercise and memory to gain a more comprehensive understanding of how these relate to one another.– Dr Sandrine Thuret, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN),King’s College London 


Researchers analysed the molecular and genetic mechanisms by exposing human NSCs to serums from either young or old individuals and to chemicals whose effects mimic the ageing process. The genes identified from the in vitro analysis as important in nutrient-sensing-pathways were then associated with genetic data from over 2000 individuals from the TwinsUK cohort and data on performance on the Paired Associates Learning (PAL) task which assesses visual memory and learning, healthy eating, Mediterranean diet, calorie intake and physical activity.

The work was supported by a grant from the Medical Research Council.

Reference: De Lucia, C. (2020) Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence Communications Biology. DOI: 10.1038/s42003-020-0844-1.




Contacts and sources: 
Franca Davenport
King's College London

Publication: Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence. Chiara de Lucia, Tytus Murphy, Claire J. Steves, Richard J. B. Dobson, Petroula Proitsi, Sandrine Thuret. Communications Biology, 2020; 3 (1) DOI: 10.1038/s42003-020-0844-1






When Three Species of Human Ancestor Walked The Earth



An international team including ASU researcher Gary Schwartz, has unearthed the earliest known skull of Homo erectus, the first of our ancestors to be nearly human-like in their anatomy and aspects of their behavior.

Years of painstaking excavation at the fossil-rich site of Drimolen, nestled within the Cradle of Humankind (a UNESCO World Heritage site located just 40 kilometers or around 25 miles northwest of Johannesburg in South Africa), has resulted in the recovery of several new and important fossils. The skull, attributed to Homo erectus, is securely dated to be two million years old.

Homo erectus cranium from Dimolen, South Africa.
 Credit Angeline Leece.

In a paper published this week in Science, the team of nearly 30 scientists from five countries share details of this skull — the most ancient fossil Homo erectus known — and other fossils from Drimolen and discuss how these new finds are forcing us to rewrite a part of our species’ evolutionary history.

The high-resolution dating of Drimolen’s fossil deposits demonstrates the age of the new skull to pre-date Homo erectus specimens from other sites within and outside of Africa by at least 100,000 to 200,000 years and thus confirms an African origin for the species.

The skull, reconstructed from more than 150 separate fragments, is of an individual likely aged between three and six years old, giving scientists a rare glimpse into childhood growth and development in these early human ancestors.

A 3D laser scan of Drimolen main quarry showing the discovery location of the new Homo erectus (DNH 134) and Paranthropus robustus (DNH 152) crania relative to the major site features and the position of the original fossil find the site (DNH 7).”


 Credit: David Strait

Additional fossils recovered from Drimolen belong to a different species — in fact, a different genus of ancient human altogether — the more heavily built, robust human ancestor Paranthropus robustus, known to also occur at several nearby cave sites preserving fossils of the same geological age. A third, distinctive species, Australopithecus sediba, is known from two-million-year old deposits of an ancient cave site virtually down the road from Drimolen.

“Unlike the situation today, where we are the only human species, two million years ago our direct ancestor was not alone,” said Andy Herries, project director and lead researcher from La Trobe University in Australia.

Gary Schwartz, a paleoanthropologist and research associate with ASU’s Institute of Human Origins, participated in the excavations and recovery of the new cranium, and as an expert in the evolution of growth and development, is continuing his work with the research team to analyze the many infant and juvenile specimens found at the site.

“What is really exciting is the discovery that during this same narrow time slice, at just around two million years ago, there were three very different types of ancient human ancestors roaming the same small landscape,” said Schwartz, who is also an associate professor in the School of Human Evolution and Social Change.. “We don’t yet know whether they interacted directly, but their presence raises the possibility that these ancient fossil humans evolved strategies to divvy up the landscape and its resources in some way to enable them to live in such close proximity.” 


Drimolen excavation site. Gary Schwartz is in the red hard hat.

Credit: Andy Herries and Giovanni Boschian

The ability to date Drimolen’s cave deposits with such a high degree of precision, using a range of different dating techniques, allowed the team to address important broader questions about human evolution in this region of Africa.

Paper co-author Justin Adams from Monash University (Australia), a specialist in reconstructing paleohabitats based on the animals preserved at fossil sites, said the discovery now allows us to address what role changing habitats, resources, and the unique biological adaptations of early Homo erectus may have played in the eventual extinction of Australopithecus sediba in South Africa.

“The discovery of the earliest Homo erectus marks a milestone for South African fossil heritage,” said Stephanie Baker, project co-director and University of Johannesburg doctoral student.

Fieldwork will continue at Drimolen, expanding the excavations to include even more ancient components of the cave and to provide a more in-depth glimpse at the forces shaping human evolution in this part of the African continent.








Contacts and sources: 
Julie Russ
Arizona State University

Publication: Contemporaneity of Australopithecus, Paranthropus, and early Homo erectus in South Africa.
Andy I. R. Herries, Jesse M. Martin, A. B. Leece, Justin W. Adams, Giovanni Boschian, Renaud Joannes-Boyau, Tara R. Edwards, Tom Mallett, Jason Massey, Ashleigh Murszewski, Simon Neubauer, Robyn Pickering, David S. Strait, Brian J. Armstrong, Stephanie Baker, Matthew V. Caruana, Tim Denham, John Hellstrom, Jacopo Moggi-Cecchi, Simon Mokobane, Paul Penzo-Kajewski, Douglass S. Rovinsky, Gary T. Schwartz, Rhiannon C. Stammers, Coen Wilson, Jon Woodhead, Colin Menter. Science, 2020; 368 (6486): eaaw7293 DOI: 10.1126/science.aaw7293







COVID-19 Vaccine Candidate Shows Promise in First Peer-Reviewed Research


University of Pittsburgh School of Medicine scientists announced a potential vaccine against SARS-CoV-2, the new coronavirus causing the COVID-19 pandemic. When tested in mice, the vaccine, delivered through a fingertip-sized patch, produces antibodies specific to SARS-CoV-2 at quantities thought to be sufficient for neutralizing the virus.



The paper appeared April 2 in eBioMedicine, which is published by The Lancet, and is the first study to be published after critique from fellow scientists at outside institutions that describes a candidate vaccine for COVID-19. The researchers were able to act quickly because they had already laid the groundwork during earlier coronavirus epidemics.

“We had previous experience on SARS-CoV in 2003 and MERS-CoV in 2014. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We knew exactly where to fight this new virus,” said co-senior author Andrea Gambotto, associate professor of surgery at the Pitt School of Medicine. “That’s why it’s important to fund vaccine research. You never know where the next pandemic will come from.”

“Our ability to rapidly develop this vaccine was a result of scientists with expertise in diverse areas of research working together with a common goal,” said co-senior author Louis Falo, professor and chair of dermatology at Pitt’s School of Medicine and UPMC.

Compared to the experimental mRNA vaccine candidate that just entered clinical trials, the vaccine described in this paper—which the authors are calling PittCoVacc, short for Pittsburgh CoronaVirus Vaccine—follows a more established approach, using lab-made pieces of viral protein to build immunity. It’s the same way the current flu shots work.

The researchers also used a novel approach to deliver the drug, called a microneedle array, to increase potency. This array is a fingertip-sized patch of 400 tiny needles that delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles—which are made entirely of sugar and the protein pieces—simply dissolve into the skin.

“We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient,” Falo
said. “And it’s actually pretty painless—it feels kind of like Velcro.”

COVID-19 Vaccine Candidate Shows Promise from University of Pittsburgh on Vimeo. https://vimeo.com/403428170

The system is also highly scalable. The protein pieces are manufactured by a “cell factory”—layers upon layers of cultured cells engineered to express the SARS-CoV-2 spike protein—that can be stacked further to multiply yield. Purifying the protein can also be done at industrial scale. Mass-producing the microneedle array involves spinning down the protein-sugar mixture into a mold using a centrifuge. Once manufactured, the vaccine can sit at room temperature until it’s needed, eliminating the need for refrigeration during transport or storage.

“For most vaccines, you don’t need to address scalability to begin with,” Gambotto said. “But when you try to develop a vaccine quickly against a pandemic that’s the first requirement.”

File:Coronavirus SARS-CoV-2.jpg
Credit: Felipe Esquivel Reed / Wikimedia Commons

When tested in mice, PittCoVacc generated a surge of antibodies against SARS-CoV-2 within two weeks of the microneedle prick.

Those animals haven’t been tracked long term yet, but the researchers point out that mice who got their MERS-CoV vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far the antibody levels of the SARS-CoV-2 vaccinated animals seem to be following the same trend.

Importantly, the SARS-CoV-2 microneedle vaccine maintains its potency even after being thoroughly sterilized with gamma radiation—a key step toward making a product that’s suitable for use in humans.

The authors are now in the process of applying for an investigational new drug (IND) approval from the Food and Drug Administration in anticipation of starting a phase I human clinical trial in the next few months.

“Testing in patients would typically require at least a year and probably longer,” Falo said. “This particular situation is different from anything we’ve ever seen, so we don’t know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster.”

Additional authors on the study are Eun Kim, Geza Erdos, Shaohua Huang, Thomas Kenniston, Stephen Balmert, Cara Donahue Carey, Michael Epperly, William Klimstra and Emrullah Korkmaz, all of Pitt; and Bart Haagmans, of Erasmus Medical Center.

Funding for this study was provided by National Institute of Allergy and Infectious Diseases grant R21-AI114264, National Institute of Arthritis and Musculoskeletal and Skin Diseases grants R01-AR074285, R01-AR071277 and R01-AR068249, and National Cancer Institute grant T32-CA175294.


Contacts and sources:
Erin Hare
University of Pittsburgh


Publication: Microneedle array delivered recombinant coronavirus vaccines:Immunogenicity and rapid translational development. Eun Kima, Geza Erdosb, Shaohua Huanga, Thomas W. Kennistona, Stephen C. Balmertb,Cara Donahue Careyb, V. Stalin Raje,1, Michael W. Epperlyc, William B. Klimstrad,Bart L. Haagmanse, Emrullah Korkmazb,f, Louis D. Falo Jr.b,f,g,h,*, Andrea Gambotto. EBioMedicine, 2020 DOI: 10.1016/j.ebiom.2020.102743






Our Direct Human Ancestor Homo Erectus Is Far Older Than We Thought


A Homo erectus skullcap found northwest of Johannesburg in South Africa has been identified as the oldest to date, in research published in Science. The hominin is a direct ancestor of modern humans, experienced a changing climate, and moved out of Africa into other continents. The discovery of DNH 134 pushes the possible origin of Homo erectus back between 150,000 and 200,000 years.

Credit: Therese van Wyk, University of Johannesburg.

An unusual skullcap and thousands of clues have created a southern twist to the story of human ancestors, in research published in Science on 3 April.

The rolling hills northwest of Johannesburg are famous for fossils of human-like creatures called hominins. Because of this, the area is known as the Cradle of Humankind.

"During our field school excavations at Drimolen, a student began uncovering a cluster of fragments. We could see that they were parts of a skull. But they weren't immediately identifiable," says Ms Stephanie Baker.

Baker is a researcher and PhD candidate at the Palaeo-Research Institute at the University of Johannesburg. She manages research at the Drimolen fossil site in the Cradle of Humankind where the fragments of DNH 134 were found.

The international team was led by researchers from La Trobe University in Australia and Washington University in St. Louis in the United States.

Fossil forensics

Fossils that are millions of years old often come out of the soil in fragments. The fragments need to be rebuilt before researchers can confidently identify what kind of animal they came from.

A Homo erectus skullcap found northwest of Johannesburg in South Africa has been identified as the oldest to date, in research published in Science. The hominin is a direct ancestor of modern humans, experienced a changing climate, and moved out of Africa into other continents. The discovery of DNH 134 pushes the possible origin of Homo erectus back between 150,000 and 200,000 years.

Credit: Therese van Wyk, University of Johannesburg.

"Over the course of the field season more and more fragments were uncovered. We began piecing them together. No one could decide what this skullcap was from, until one night it all came together - and we realised we were looking at a hominin!" she says. They named the skullcap DNH 134.

The next question was - what kind of hominin? The Cradle of Humankind has several different species of human ancestors and the Drimolen site had at least two kinds.

"This find really challenged us. We compared the assembled skullcap to all of the other examples of hominins in the Cradle area. Eventually, its teardrop shape and relatively big brain cavity meant we were looking at Homo erectus," says Baker.

Homo erectus is one of our direct human ancestors and is best known for migrating out of Africa into the rest of the world.

These hominins walked upright and were a more human-like species than the other hominins found in the Cradle. They had shorter arms and longer legs. They could walk and run for longer distances over the African grasslands than the others.

How old?

Once the question of 'which species?' was answered, two other huge questions presented themselves. How long ago was this individual alive? And how old were they when they died?

The researchers knew that no other Homo erectus fossils had ever been found in South Africa before. Even more surprising was the time period suggested by the soil layers the skull fragments were found in. "Before we found DNH 134, we knew that the oldest Homo erectus in the world was from Dmanisi in Georgia dating to 1.8 million years ago," says Baker.

Building a 3D puzzle over time

Trying to figure out how old fossils are from the caves west of Johannesburg is quite tricky. There were no volcanoes during the time of the hominins, so there are no ash layers to give the researchers quick age estimates, like they use for eastern African sites.

One of our direct human ancestors is older than we thought. The Cradle of Humankind northwest of Johannesburg, South Africa has yielded its first Homo erectus fossil, and the oldest found anywhere. Homo erectus experienced a changing climate, and moved out of Africa into other continents. The discovery of skullcap DNH 134 pushes the possible origin of Homo erectus back between 150,000 and 200,000 years. 
Credit: Therese van Wyk, University of Johannesburg.

But while they were uncovering the fragments at Drimolen, they kept and recorded every clue they could find. This included fragments of small animals like bats and lizards, but also things like soil samples.

They can also tell exactly where in 3D-space in the Drimolen quarry each little fossil fragment was found.

Then the research team used every possible dating technique available to get the most accurate possible date for the deposit. This included Palaeomagnetic dating, Electron spin resonance, Uranium lead dating, and faunal dating.

Possible shifted, earlier origin

"We collated all of the dates from each of these techniques and together they showed that we had a very precise age. We now know that the Drimolen Main Quarry and all of the fossils in it, are dated from 2.04 to 1.95 million years ago," says Baker.

That means that DNH 134 is much older than the next oldest Homo erectus in Africa; and from Georgia.

"The age of the DNH 134 fossil shows that Homo erectus existed 150,000 to 200,000 years earlier than previously thought," says Professor Andy Herries. Herries is the project co-director with Ms Baker and lead researcher. He is Head of the Department of Archaeology and History, at La Trobe University in Australia and an associate in the Palaeo-Research Institute at UJ.

Because Homo erectus is one of our direct ancestors, the discovery has implications for the origins of modern humans.

"Until this find, we always assumed Homo erectus originated from eastern Africa. But DNH 134 shows that Homo erectus, one of our direct ancestors, possibly comes from southern Africa instead. That would mean that they later moved northwards into East Africa. From there they went through North Africa to populate the rest of the world," says Baker.

The skull is also unusual because it is the skull of a young Homo erectus.

"The Homo erectus skull we found, was likely aged between two and three years old when it died," says Herries.

Sharing a landscape

The age of the DNH 134 skullcap shows something else - that three species of early human ancestor lived in southern Africa at the same time at the Drimolen fossil site.

The 2.61 million year old Drimolen Makondo fossil bearing palaeocave in South Africa

Credit: Andy Herries / Wikimedia Commons


"We can now say Homo erectus shared the landscape with two other types of humans in South Africa, Paranthropus and Australopithecus," says Herries.
This might mean they needed to use different parts of the landscape to avoid competing with one another. For a start, they looked different.

Paranthropus robustus hominins were shorter than Homo erectus and Australopithecus, says Baker.

"Paranthropus robustus ate things like roots and tubers, which is why their teeth are really big. They used their enormous teeth for grinding down what we call fall-back foods - tough hard plants."

Changing weather

In comparison to the other two species, Homo erectus hominins were tall and slender. They ate things which are easier to digest, like fruits and berries.

"We also know that they were eating meat, but we aren't exactly sure how they were getting it yet. We can say that at least these early Homo erectus weren't hunting with any weaponry yet," says Baker.

"We also know that they were able to cover long distances. Which turned out lucky for them, because during their time, the climate changed in southern Africa.

Paranthropus and Australopithecus evolved in warm and humid climates and were used to that. But then the weather began to shift from warm and humid, to cool and dry," she says.

Gradually the tree-cover diminished, and grasses took their place. Eventually the forests were replaced with the African savannah grasslands of today. The cooler weather suited the more mobile and social Homo erectus better. But it meant that Paranthropus had to rely on less desirable foods.


Contacts and sources: 
Therese van Wyk
University of Johannesburg



Publication: Contemporaneity of Australopithecus, Paranthropus, and early Homo erectus in South Africa Science  03 Apr 2020: Vol. 368, Issue 6486, eaaw7293 DOI: 10.1126/science.aaw7293   http://dx.doi.org/10.1126/science.aaw7293






Discovery of Life in Solid Rock Deep Beneath Sea May Inspire New Search for Life on Mars



Bacteria live in tiny clay-filled cracks in solid rock millions of years old.

Aerobic bacteria live densely packed into tunnels of clay minerals found in this sample of solid rock, collected from 122 meters beneath the seafloor. Image B is 1,000 times greater magnification than Image A. The left side photo in each image was taken using normal light and the right side photo was taken using fluorescent light. The solid basalt rock is gray, the clay minerals are orange, and the bacterial cells are green spheres.
Credit: Suzuki et al. 2020, DOI: 10.1038/s42003-020-0860-1, CC BY 4.0

Newly discovered single-celled creatures living deep beneath the seafloor have given researchers clues about how they might find life on Mars. These bacteria were discovered living in tiny cracks inside volcanic rocks after researchers persisted over a decade of trial and error to find a new way to examine the rocks.

Associate Professor Yohey Suzuki at the University of Tokyo led the effort to develop a new way to prepare rock samples to search for life deep beneath the seafloor. This is an example of one of the thin slices of rock he prepared using special epoxy to ensure the rock held its shape while it was cut.

Credit: Caitlin Devor, University of Tokyo, CC BY 4.0

Researchers estimate that the rock cracks are home to a community of bacteria as dense as that of the human gut, about 10 billion bacterial cells per cubic centimeter (0.06 cubic inch). In contrast, the average density of bacteria living in mud sediment on the seafloor is estimated to be 100 cells per cubic centimeter.

"I am now almost over-expecting that I can find life on Mars. If not, it must be that life relies on some other process that Mars does not have, like plate tectonics," said Associate Professor Yohey Suzuki from the University of Tokyo, referring to the movement of land masses around Earth most notable for causing earthquakes. Suzuki is first author of the research paper announcing the discovery, published in Communications Biology.

Magic of clay minerals

"I thought it was a dream, seeing such rich microbial life in rocks," said Suzuki, recalling the first time he saw bacteria inside the undersea rock samples.

Undersea volcanoes spew out lava at approximately 1,200 degrees Celsius (2,200 degrees Fahrenheit), which eventually cracks as it cools down and becomes rock. The cracks are narrow, often less than 1 millimeter (0.04 inch) across. Over millions of years, those cracks fill up with clay minerals, the same clay used to make pottery. Somehow, bacteria find their way into those cracks and multiply.

"These cracks are a very friendly place for life. Clay minerals are like a magic material on Earth; if you can find clay minerals, you can almost always find microbes living in them," explained Suzuki.

The microbes identified in the cracks are aerobic bacteria, meaning they use a process similar to how human cells make energy, relying on oxygen and organic nutrients.

"Honestly, it was a very unexpected discovery. I was very lucky, because I almost gave up," said Suzuki.

Cruise for deep ocean samples

Suzuki and his colleagues discovered the bacteria in rock samples that he helped collect in late 2010 during the Integrated Ocean Drilling Program (IODP). IODP Expedition 329 took a team of researchers from the tropical island of Tahiti in the middle of the Pacific Ocean to Auckland, New Zealand. The research ship anchored above three locations along the route across the South Pacific Gyre and used a metal tube 5.7 kilometers long to reach the ocean floor. Then, a drill cut down 125 meters below the seafloor and pulled out core samples, each about 6.2 centimeters across. The first 75 meters beneath the seafloor were mud sediment and then researchers collected another 40 meters of solid rock.

Depending on the location, the rock samples were estimated to be 13.5 million, 33.5 million and 104 million years old. The collection sites were not near any hydrothermal vents or sub-seafloor water channels, so researchers are confident the bacteria arrived in the cracks independently rather than being forced in by a current. The rock core samples were also sterilized to prevent surface contamination using an artificial seawater wash and a quick burn, a process Suzuki compares to making aburi (flame-seared) sushi.

At that time, the standard way to find bacteria in rock samples was to chip away the outer layer of the rock, then grind the center of the rock into a powder and count cells out of that crushed rock.

"I was making loud noises with my hammer and chisel, breaking open rocks while everyone else was working quietly with their mud," he recalled.

How to slice a rock

Over the years, continuing to hope that bacteria might be present but unable to find any, Suzuki decided he needed a new way to look specifically at the cracks running through the rocks. He found inspiration in the way pathologists prepare ultrathin slices of body tissue samples to diagnose disease. Suzuki decided to coat the rocks in a special epoxy to support their natural shape so that they wouldn't crumble when he sliced off thin layers.

These thin sheets of solid rock were then washed with dye that stains DNA and placed under a microscope.

The bacteria appeared as glowing green spheres tightly packed into tunnels that glow orange, surrounded by black rock. That orange glow comes from clay mineral deposits, the "magic material" giving bacteria an attractive place to live.

Whole genome DNA analysis identified the different species of bacteria that lived in the cracks. Samples from different locations had similar, but not identical, species of bacteria. Rocks at different locations are different ages, which may affect what minerals have had time to accumulate and therefore what bacteria are most common in the cracks.

Suzuki and his colleagues speculate that the clay mineral-filled cracks concentrate the nutrients that the bacteria use as fuel. This might explain why the density of bacteria in the rock cracks is eight orders of magnitude greater than the density of bacteria living freely in mud sediment where seawater dilutes the nutrients.

From the ocean floor to Mars

The clay minerals filling cracks in deep ocean rocks are likely similar to the minerals that may be in rocks now on the surface of Mars.

"Minerals are like a fingerprint for what conditions were present when the clay formed. Neutral to slightly alkaline levels, low temperature, moderate salinity, iron-rich environment, basalt rock -- all of these conditions are shared between the deep ocean and the surface of Mars," said Suzuki.

Suzuki's research team is beginning a collaboration with NASA's Johnson Space Center to design a plan to examine rocks collected from the Martian surface by rovers. Ideas include keeping the samples locked in a titanium tube and using a CT (computed tomography) scanner, a type of 3D X-ray, to look for life inside clay mineral-filled cracks.

"This discovery of life where no one expected it in solid rock below the seafloor may be changing the game for the search for life in space," said Suzuki.


Graduate School of Science: https://www.s.u-tokyo.ac.jp/en/

Yohey Suzuki research introduction video: https://www.youtube.com/watch?v=Ezw193eNlcg

 

Contacts and sources: 
Yohey Suzuki / Ms. Caitlin Devor
University of Tokyo

Publication:   Yohey Suzuki, Seiya Yamashita, Mariko Kouduka, Yutaro Ao, Hiroki Mukai, Satoshi Mitsunobu, Hiroyuki Kagi3, Steven D' Hondt, Fumio Inagaki, Yuki Morono, Tatsuhiko Hoshino, Naotaka Tomioka, Motoo Ito. Deep microbial proliferation at the basalt interface in 33.5-104 million-year-old oceanic crust. 2 April 2020. Communications Biology. DOI: 10.1038/s42003-020-0860-1.





Thursday, April 2, 2020

Trial Drug Can Significantly Block Early Stages of COVID-19 in Engineered Human Tissues




‘There is hope for this horrible pandemic,’ says UBC scientist Dr. Josef Penninger

An international team led by University of British Columbia researcher Dr. Josef Penninger has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts.

In cell cultures analyzed in the current study, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000.
Drug can significantly block early stages of COVID-19 in engineered human tissues
 Credit: IMBA/Tibor Kulcsar


The findings, published today in Cell, hold promise as a treatment capable of stopping early infection of the novel coronavirus that, as of April 2, has affected more than 981,000 people and claimed the lives of 50,000 people worldwide.

Josef Penninger

Credit: UBC

The study provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19, and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys.

“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic,” says Penninger, professor in UBC’s faculty of medicine, director of the Life Sciences Institute and the Canada 150 Research Chair in Functional Genetics at UBC.

“This work stems from an amazing collaboration among academic researchers and companies, including Dr. Ryan Conder’s gastrointestinal group at STEMCELL Technologies in Vancouver, Nuria Montserrat in Spain, Drs. Haibo Zhang and Art Slutsky from Toronto and especially Ali Mirazimi’s infectious biology team in Sweden, who have been working tirelessly day and night for weeks to better understand the pathology of this disease and to provide breakthrough therapeutic options.”

ACE2 — a protein on the surface of the cell membrane — is now at centre-stage in this outbreak as the key receptor for the spike glycoprotein of SARS-CoV-2. In earlier work, Penninger and colleagues at the University of Toronto and the Institute of Molecular Biology in Vienna first identified ACE2, and found that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003. His laboratory also went on to link the protein to both cardiovascular disease and lung failure.

While the COVID-19 outbreak continues to spread around the globe, the absence of a clinically proven antiviral therapy or a treatment specifically targeting the critical SARS-CoV-2 receptor ACE2 on a molecular level has meant an empty arsenal for health care providers struggling to treat severe cases of COVID-19.

Illustration of engineered replicas of human blood vessels and kidneys grown from stem cells being treated with hrsACE2. 
Image credit: IMBA/Tibor Kulcsar

“Our new study provides very much needed direct evidence that a drug — called APN01 (human recombinant soluble angiotensin-converting enzyme 2 – hrsACE2) — soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” says Dr. Art Slutsky, a scientist at the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital and professor at the University of Toronto who is a collaborator on the study.

In cell cultures analyzed in the current study, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000. In engineered replicas of human blood vessel and kidneys — organoids grown from human stem cells — the researchers demonstrated that the virus can directly infect and duplicate itself in these tissues. This provides important information on the development of the disease and the fact that severe cases of COVID-19 present with multi-organ failure and evidence of cardiovascular damage. Clinical grade hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues.

“Using organoids allows us to test in a very agile way treatments that are already being used for other diseases, or that are close to being validated. In these moments in which time is short, human organoids save the time that we would spend to test a new drug in the human setting,” says Núria Montserrat, ICREA professor at the Institute for Bioengineering of Catalonia in Spain.

“The virus causing COVID-19 is a close sibling to the first SARS virus,” adds Penninger. “Our previous work has helped to rapidly identify ACE2 as the entry gate for SARS-CoV-2, which explains a lot about the disease. Now we know that a soluble form of ACE2 that catches the virus away, could be indeed a very rational therapy that specifically targets the gate the virus must take to infect us. There is hope for this horrible pandemic.”

This research was supported in part by the Canadian federal government through emergency funding focused on accelerating the development, testing, and implementation of measures to deal with the COVID-19 outbreak.



Contacts and sources: 
Thandi Fletcher
University of British Columbia

Publication:  Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Vanessa Monteil, Hyesoo Kwon, Patricia Prado, Astrid Hagelkrüys, Reiner A. Wimmer, Martin Stahl, Alexandra Leopoldi, Elena Garreta, Carmen Hurtado Del Pozo, Felipe Prosper, J.p. Romero, Gerald Wirnsberger, Haibo Zhang, Arthur S. Slutsky, Ryan Conder, Nuria Montserrat, Ali Mirazimi, Josef M. Penninger. Submitted to Cell, 2020 DOI: 10.1016/j.cell.2020.04.004

A Possible Treatment for COVID-19 and an Approach for Developing Others

SARS-CoV-2, the virus that causes COVID-19 disease is more transmissible, but has a lower mortality rate than its sibling, SARS-CoV, according to a review article published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

As of March 11, more than 120,000 cases of the rapidly spreading COVID-19 have been confirmed worldwide, along with more than 4,000 deaths.

In humans, coronaviruses cause mainly respiratory infections. Individuals with SARS-CoV-2 may remain asymptomatic for 2 to 14 days post-infection and some individuals likely transmit the virus without developing disease symptoms.

SARS-CoV-2 virus illustration
Credit: We Are Covert / Wikimedia Commons

So far, the most promising compound for treating COVID-19 is the antiviral, remdesivir. It is currently in clinical trials for treating Ebola virus infections.

Remdesivir was recently tested in a non-human primate model of MERS-CoV infection. Prophylactic treatment 24 hours prior to inoculation prevented MERS-CoV from causing clinical disease and inhibited viral replication in lung tissues, preventing formation of lung lesions. Initiation of treatment 12 hours after virus inoculation was similarly effective.

Remdesivir has also shown effectiveness against a wide range of coronaviruses. It has already undergone safety testing in clinical trials for Ebola, thereby reducing the time that would be necessary for conducting clinical trials for SARS-CoV-2.

Nonetheless, much work needs to be done to gain a better understanding of the mechanics of SARS-CoV-2. For example, understanding how SARS-CoV-2 interacts with the host ACE2 receptor—by which SARS-CoV-2 gains entry into the host (whether human or animal)—might reveal how this virus overcame the species barrier between animals and humans. This could also lead to design of new antivirals.

Although coronaviruses are common in bats, no direct animal source of the epidemic has been identified to date, according to the report. “It is critical to identify the intermediate species to stop the current spread and to prevent future human SARS-related coronavirus epidemics,” the researchers write.


Contacts and sources:
American Society for Microbiology


Publication: Miguel Angel Martinez. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrobial Agents and Chemotherapy, 2020; DOI: 10.1128/AAC.00399-20

Regular Exercise Benefits Immunity – Even in Isolation


New analysis highlights the power of regular, daily exercise on our immune system and the importance of people continuing to work-out even in lockdown.

Being in isolation without access to gyms and sports clubs should not mean people stop exercising, according to a new study from researchers at the University of Bath. Keeping up regular, daily exercise at a time when much of the world is going into isolation will play an important role in helping to maintain a healthy immune system.

The analysis, published in the international journal Exercise Immunology Review, involving leading physiologists Dr James Turner and Dr John Campbell from the University of Bath’s Department for Health, considers the effect of exercise on our immune function.

Credit: John Robert McPherson - / Wikimedia Commons

Over the last four decades, many studies have investigated how exercise affects the immune system. It is widely agreed that regular moderate intensity exercise is beneficial for immunity, but a view held by some is that more arduous exercise can suppress immune function, leading to an ‘open-window’ of heightened infection risk in the hours and days following exercise.

In a benchmark study in 2018, this ‘open window’ hypothesis was challenged by Dr Campbell and Dr Turner. They reported in a review article that the theory was not well supported by scientific evidence, summarizing that there is limited reliable evidence that exercise suppresses immunity, concluding instead that exercise is beneficial for immune function.

They say that, in the short term, exercise can help the immune system find and deal with pathogens, and in the long term, regular exercise slows down changes that happen to the immune system with ageing, therefore reducing the risk of infections.

In a new article, published this month, leading experts, including Dr Turner and Dr Campbell, debated whether the immune system can change in a negative or positive way after exercise, and whether or not athletes get more infections than the general population. The article concludes that infections are more likely to be linked to inadequate diet, psychological stress, insufficient sleep, travel and importantly, pathogen exposure at social gathering events like marathons - rather than the act of exercising itself.

Author Dr James Turner from our Department for Health explains: “Our work has concluded that there is very limited evidence for exercise directly increasing the risk of becoming infected with viruses. In the context of coronavirus and the conditions we find ourselves in today, the most important consideration is reducing your exposure from other people who may be carrying the virus. But people should not overlook the importance of staying fit, active and healthy during this period. Provided it is carried out in isolation - away from others - then regular, daily exercise will help better maintain the way the immune system works – not suppress it.”

Co-author, Dr John Campbell added: “People should not fear that their immune system will be suppressed by exercise placing them at increased risk of Coronavirus. Provided exercise is carried out according to latest government guidance on social distancing, regular exercise will have a tremendously positive effect on our health and wellbeing, both today and for the future.”

Regular moderate intensity aerobic exercise, such as walking, running or cycling is recommended, with the aim of achieving 150 minutes per week. Longer, more vigorous exercise would not be harmful, but if capacity to exercise is restricted due to a health condition or disability, the message is to ‘move more’ and that ‘something is better than nothing’. Resistance exercise has clear benefits for maintaining muscles, which also helps movement.

At this current time in particular, the researchers underline the importance of maintaining good personal hygiene when exercising, including thoroughly washing hands following exercise. To give the body its best chance at fighting off infections, they suggest in addition to doing regular exercise, people need to pay attention to the amount of sleep they get and maintain a healthy diet, that is energy balanced to account for energy that is used during exercise. They hope that this debate article will lead to a wave of new research exploring the beneficial effects of exercise on immune function.




Contacts and sources:
Andy Dunne
University of Bath

Publication: Can Exercise Affect Immune Function to Increase Susceptibility to Infection? Richard J Simpson, John P Campbell, Maree Gleeson, Karsten Krüger, David C Nieman, David B Pyne, James E Turner, Neil P Walsh. Exerc Immunol Rev, 2020




Wednesday, April 1, 2020

Hubble Finds Best Evidence for Elusive Mid-Sized Black Hole



Astronomers have found the best evidence for the perpetrator of a cosmic homicide: a black hole of an elusive class known as "intermediate-mass," which betrayed its existence by tearing apart a wayward star that passed too close.

Weighing in at about 50,000 times the mass of our Sun, the black hole is smaller than the supermassive black holes (at millions or billions of solar masses) that lie at the cores of large galaxies, but larger than stellar-mass black holes formed by the collapse of a massive star.

 This illustration depicts a cosmic homicide in action. A wayward star is being shredded by the intense gravitational pull of a black hole that contains tens of thousands of solar masses. The stellar remains are forming an accretion disk around the black hole. Flares of X-ray light from the super-heated gas disk alerted astronomers to the black hole's location; otherwise it lurked unknown in the dark. The elusive object is classified as an intermediate mass black hole (IMBH), as it is much less massive than the monster black holes that dwell in the centers of galaxies. Therefore, IMBHs are mostly quiescent because they do not pull in as much material, and are hard to find. Hubble observations provide evidence that the IMBH dwells inside a dense star cluster. The cluster itself may be the stripped-down core of a dwarf galaxy. 
illustration of a glowing black hole accretion disk with material spiraling into it.
Credit: NASA, ESA and D. Player (STScI)

These so-called intermediate-mass black holes (IMBHs) are a long-sought "missing link" in black hole evolution. Though there have been a few other IMBH candidates, researchers consider these new observations the strongest evidence yet for mid-sized black holes in the universe.

It took the combined power of two X-ray observatories and the keen vision of NASA's Hubble Space Telescope to nail down the cosmic beast.

Astronomers have found the best evidence for a black hole of an elusive class known as “intermediate-mass,” which betrayed its existence by tearing apart a wayward star that passed too close. This exciting discovery opens the door to the possibility of many more lurking undetected in the dark, waiting to be given away by a star passing too close.

Credits: NASA's Goddard Space Flight Center

"Intermediate-mass black holes are very elusive objects, and so it is critical to carefully consider and rule out alternative explanations for each candidate. That is what Hubble has allowed us to do for our candidate," said Dacheng Lin of the University of New Hampshire, principal investigator of the study. The results are published on March 31, 2020, in The Astrophysical Journal Letters.

The story of the discovery reads like a Sherlock Holmes story, involving the meticulous step-by-step case-building necessary to catch the culprit.

Lin and his team used Hubble to follow up on leads from NASA's Chandra X-ray Observatory and ESA's (the European Space Agency) X-ray Multi-Mirror Mission (XMM-Newton). In 2006 these satellites detected a powerful flare of X-rays, but they could not determine whether it originated from inside or outside of our galaxy. Researchers attributed it to a star being torn apart after coming too close to a gravitationally powerful compact object, like a black hole.

Surprisingly, the X-ray source, named 3XMM J215022.4−055108, was not located in a galaxy's center, where massive black holes normally would reside. This raised hopes that an IMBH was the culprit, but first another possible source of the X-ray flare had to be ruled out: a neutron star in our own Milky Way galaxy, cooling off after being heated to a very high temperature. Neutron stars are the crushed remnants of an exploded star.

This Hubble Space Telescope image identified the location of an intermediate-mass black hole, weighing 50,000 times the mass of our Sun (making it much smaller than supermassive black holes found in the centers of galaxies). The black hole, named 3XMM J215022.4−055108, is indicated by the white circle. The elusive type of black hole was first identified in a burst of telltale X-rays emitted by hot gas from a star as it was captured and destroyed by the black hole. Hubble was needed to pinpoint the black hole's location in visible light. Hubble's deep, high-resolution imaging shows that the black hole resides inside a dense cluster of stars that is far beyond our Milky Way galaxy. The star cluster is in the vicinity of the galaxy at the center of the image. Much smaller-looking background galaxies appear sprinkled around the image, including a face-on spiral just above the central foreground galaxy. This photo was taken with Hubble's Advanced Camera for Surveys.


Credits: NASA, ESA and D. Lin (University of New Hampshire)


Hubble was pointed at the X-ray source to resolve its precise location. Deep, high-resolution imaging provides strong evidence that the X-rays emanated not from an isolated source in our galaxy, but instead in a distant, dense star cluster on the outskirts of another galaxy — just the type of place astronomers expected to find an IMBH. Previous Hubble research has shown that the mass of a black hole in the center of a galaxy is proportional to that host galaxy's central bulge. In other words, the more massive the galaxy, the more massive its black hole. Therefore, the star cluster that is home to 3XMM J215022.4−055108 may be the stripped-down core of a lower-mass dwarf galaxy that has been gravitationally and tidally disrupted by its close interactions with its current larger galaxy host.

IMBHs have been particularly difficult to find because they are smaller and less active than supermassive black holes; they do not have readily available sources of fuel, nor as strong a gravitational pull to draw stars and other cosmic material which would produce telltale X-ray glows. Astronomers essentially have to catch an IMBH red-handed in the act of gobbling up a star. Lin and his colleagues combed through the XMM-Newton data archive, searching hundreds of thousands of observations to find one IMBH candidate.

The X-ray glow from the shredded star allowed astronomers to estimate the black hole's mass of 50,000 solar masses. The mass of the IMBH was estimated based on both X-ray luminosity and the spectral shape. "This is much more reliable than using X-ray luminosity alone as typically done before for previous IMBH candidates," said Lin. "The reason why we can use the spectral fits to estimate the IMBH mass for our object is that its spectral evolution showed that it has been in the thermal spectral state, a state commonly seen and well understood in accreting stellar-mass black holes."

This object isn't the first to be considered a likely candidate for an intermediate-mass black hole. In 2009 Hubble teamed up with NASA's Swift observatory and ESA's XMM-Newton to identify what is interpreted as an IMBH, called HLX-1, located towards the edge of the galaxy ESO 243-49. It too is in the center of a young, massive cluster of blue stars that may be a stripped-down dwarf galaxy core. The X-rays come from a hot accretion disk around the black hole. "The main difference is that our object is tearing a star apart, providing strong evidence that it is a massive black hole, instead of a stellar-mass black hole as people often worry about for previous candidates including HLX-1," Lin said.

Finding this IMBH opens the door to the possibility of many more lurking undetected in the dark, waiting to be given away by a star passing too close. Lin plans to continue his meticulous detective work, using the methods his team has proved successful. Many questions remain to be answered. Does a supermassive black hole grow from an IMBH? How do IMBHs themselves form? Are dense star clusters their favored home?

The Hubble Space Telescope is a project of international cooperation between NASA and ESA (European Space Agency). NASA's Goddard Space Flight Center in Greenbelt, Maryland, manages the telescope. The Space Telescope Science Institute (STScI) in Baltimore, Maryland, conducts Hubble science operations. STScI is operated for NASA by the Association of Universities for Research in Astronomy in Washington, D.C.




Contacts and sources:
Claire Andreoli
NASA's Goddard Space Flight Center, Greenbelt, Md.

Leah Ramsay / Ray Villard
Space Telescope Science Institute, Baltimore

Dacheng Lin
University of New Hampshire, Durham


Publication:





Where in the Brain Does Creativity Come from? Evidence from Jazz Musicians

Where does creativity come from?

According to a popular view, creativity is a product of the brain’s right hemisphere – innovative people are considered “right-brain thinkers” while “left-brain thinkers” are thought to be analytical and logical. Neuroscientists who are skeptical of this idea have argued that there is not enough evidence to support this idea and an ability as complex as human creativity must draw on vast swaths of both hemispheres. A new brain-imaging study out of Drexel University’s Creativity Research Lab sheds light on this controversy by studying the brain activity of jazz guitarists during improvisation.

The study, which was recently published in the journal NeuroImage, showed that creativity is, in fact, driven primarily by the right hemisphere in musicians who are comparatively inexperienced at improvisation. However, musicians who are highly experienced at improvisation rely primarily on their left hemisphere. This suggests that creativity is a “right-brain ability” when a person deals with an unfamiliar situation but that creativity draws on well-learned, left-hemisphere routines when a person is experienced at the task.

Figure 1: Jazz guitar player improvising while his brain activity (EEG) is recorded.

Credit: Drexel University
By taking into consideration how brain activity changes with experience, this research may contribute to the development of new methods for training people to be creative in their field. For instance, when a person is an expert, his or her performing is produced primarily by relatively unconscious, automatic processes that are difficult for a person to consciously alter, but easy to disrupt in the attempt, as when self-consciousness causes a person to “choke” or falter.

In contrast, novices’ performances tend to be under deliberate, conscious control. Thus, they are better able to make adjustments according to instructions given by a teacher or coach. Recordings of brain activity could reveal the point at which a performer is ready to release some conscious control and rely on unconscious, well-learned routines. Releasing conscious control prematurely may cause the performer to lock-in bad habits or nonoptimal technique.

The study was led by David Rosen, PhD, a recent Drexel doctoral graduate and current co-founder and chief operations officer of Secret Chord Laboratories, a music-technology startup company; and John Kounios, PhD, professor of psychology and director of the doctoral program in applied and cognitive brain sciences in Drexel’s College of Arts and Sciences.

The team recorded high-density electroencephalograms (EEGs) from 32 jazz guitar players, some of whom were highly experienced and others less experienced. Each musician improvised to six jazz lead sheets (songs) with programmed drums, bass and piano accompaniment. The 192 recorded jazz improvisations (six jazz songs by 32 participants) were subsequently played for four expert jazz musicians and teachers individually so they could rate each for creativity and other qualities.

The researchers compared the EEGs recorded during highly rated performances with EEGs recorded during performances that were rated to be less creative. For highly rated performances compared with less-creative performances, there was greater activity in posterior left-hemisphere areas of the brain; for performances with lower ratings compared with those with higher ratings, there was greater activity in right-hemisphere, mostly frontal, areas.

By themselves, these results might suggest that highly creative performances are associated with posterior left-hemisphere areas and that less-creative performances are associated with right-hemisphere areas. This pattern is misleading, however, according to the researchers, because it does not take experience of the musician into consideration.

Figure 2: Brain activity maps showing areas associated with high-creativity performances compared with lower-creativity performances. Each map shows a top view of the head.

Credit: Drexel University

Some of these musicians were highly experienced, having given many public performances over decades. Other musicians were much less experienced, having given only a very small number of public performances. When the researchers reanalyzed the EEGs to statistically control for the level of experience of the performers, a very different pattern of results emerged. Virtually all of the brain-activity differences between highly creative and less-creative performances were found in the right hemisphere, mostly in the frontal region.

This finding is in line with the team’s other research that used electrical stimulation to study how creative expression is generated in musicians’ brains and its study of how experienced and inexperienced jazz musicians reacted to being exhorted to play “even more creatively.”

The new study reveals the brain areas that support creative musical improvisation for highly experienced musicians and their less-experienced counterparts and addresses the controversial question of the roles of the left and right hemispheres in creativity. Furthermore, it raises an important issue that goes to the heart of the definition and understanding of creativity.

“If creativity is defined in terms of the quality of a product, such as a song, invention, poem or painting, then the left hemisphere plays a key role,” said Kounios. “However, if creativity is understood as a person’s ability to deal with novel, unfamiliar situations, as is the case for novice improvisers, then the right hemisphere plays the leading role.”

The study, “Dual-Process Contributions to Creativity in Jazz Improvisations: An SPM-EEG Study” was funded by a grant from the National Science Foundation. It was published in the journal NeuroImage. Co-authors included Yongtaek Oh, doctoral student; Brian Erickson, post-doctoral researcher; Fengqing (Zoe) Zhang, PhD; and Youngmoo Kim, PhD, of Drexel.







Contacts and sources:
Annie Korp
Drexel University

Publication: Dual-process contributions to creativity in jazz improvisations: An SPM-EEG study. David S. Rosen, Yongtaek Oh, Brian Erickson, Fengqing (Zoe) Zhang, Youngmoo E. Kim, John Kounios. NeuroImage, 2020; 213: 116632 DOI: 10.1016/j.neuroimage.2020.116632




Missing Link in Coronavirus Jump from Bats to Humans Could Be Pangolins, Not Snakes



As scientists scramble to learn more about the SARS-CoV-2 coronavirus, two recent studies of the virus’ genome reached controversial conclusions: namely, that snakes are intermediate hosts of the new virus, and that a key coronavirus protein shares “uncanny similarities” with an HIV-1 protein. Now, a study in ACS’ Journal of Proteome Research refutes both ideas and suggests that scaly, anteater-like animals called pangolins are the missing link for SARS-CoV-2 transmission between bats and humans.

 Pangolin
Credit:

Understanding where SARS-CoV-2 –– the virus that caused the COVID-19 pandemic ­–– came from and how it spreads is important for its control and treatment. Most experts agree that bats are a natural reservoir of SARS-CoV-2, but an intermediate host was needed for it to jump from bats to humans. A recent study that analyzed the new virus’ genome suggested snakes as this host, despite the fact that coronaviruses are only known to infect mammals and birds. 

Meanwhile, an unrelated study compared the sequence of the spike protein –– a key protein responsible for getting the virus into mammalian cells –– of the new coronavirus to that of HIV-1, noting unexpected similarities. Although the authors withdrew this preprint manuscript after scientific criticism, it spawned rumors and conspiracy theories that the new coronavirus could have been engineered in a lab. Yang Zhang and colleagues wanted to conduct a more careful and complete analysis of SARS-CoV-2 DNA and protein sequences to resolve these issues.

Compared to the previous studies, the researchers used larger data sets and newer, more accurate bioinformatics methods and databases to analyze the SARS-CoV-2 genome. They found that, in contrast to the claim that four regions of the spike protein were uniquely shared between SARS-CoV-2 and HIV-1, the four sequence segments could be found in other viruses, including bat coronavirus. After uncovering an error in the analysis that suggested snakes as an intermediate host, the team searched DNA and protein sequences isolated from pangolin tissues for ones similar to SARS-CoV-2.

The researchers identified protein sequences in sick animals’ lungs that were 91% identical to the human virus’ proteins. Moreover, the receptor binding domain of the spike protein from the pangolin coronavirus had only five amino acid differences from SARS-CoV-2, compared with 19 differences between the human and bat viral proteins. This evidence points to the pangolin as the most likely intermediate host for the new coronavirus, but additional intermediate hosts could be possible, the researchers say.

The authors acknowledge funding from the National Science Foundation, the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases and the Extreme Science and Engineering Discovery Environment.


Contacts and sources:
American Chemical Society

Publication: “Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1”Journal of Proteome Research




Median Incubation Period for COVID-19 Just Over 5 Days, Symptoms Appears within 11.5 Days



A University of Massachusetts Amherst biostatistician who directs the UMass-based Flu Forecasting Center of Excellence was invited by the White House Coronavirus Task Force to participate Wednesday morning in a coronavirus modeling webinar.

The four-hour, virtual gathering will include 20 of the world’s leading infectious disease and pandemic forecasting modelers, from researchers at Harvard, Johns Hopkins and the Centers for Disease Control and Prevention (CDC) in the U.S. to those based at institutions in England, Hong Kong, South Africa and the Netherlands.
coronavirus
Image credit: Alissa Eckert, MS; Dan Higgins, MAM

According to the White House Coronavirus Task Force coordinator Dr. Charles Vitek, “This webinar is designed to highlight for the Task Force what modeling can tell us regarding the potential effects of mitigation measures on the coronavirus outbreak. The unprecedented speed and impact of the nCoV-19 epidemic requires the best-informed public health decision-making we can produce.”

Nicholas Reich, associate professor in the School of Public Health and Health Sciences, heads a flu forecasting collaborative that has produced some of the world’s most accurate models in recent years. He and postdoctoral researcher Thomas McAndrew have been conducting weekly surveys of more than 20 infectious disease modeling researchers to assess their collective expert opinion on the trajectory of the COVID-19 outbreak in the U.S. The researchers and modeling experts design, build and interpret models to explain and understand infectious disease dynamics and the associated policy implications in human populations.

Reich is co-author of a new study in the Annals of Internal Medicine that calculates that the median incubation period for COVID-19 is just over five days and that 97.5 percent of people who develop symptoms will do so within 11.5 days of infection. The incubation period refers to the time between exposure to the virus and the appearance of the first symptoms.
Symptoms & Testing

Credit: NIH

The study’s lead author is UMass Amherst biostatistics doctoral alumnus Stephen Lauer, a former member of the Reich Lab and current postdoctoral researcher at the Johns Hopkins Bloomberg School of Public Health.

The researchers examined 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. They conclude that “the current period of active monitoring recommended by the U.S. Centers for Disease Control and Prevention [14 days] is well supported by the evidence.”

Last fall, Reich received a grant of up to $3 million over the next five years from the CDC to operate the Flu Forecasting Center of Excellence at UMass Amherst, one of two in the nation the CDC has designated.

The center’s mission is to identify new methods and data sources to sharpen the accuracy and improve communication of seasonal and pandemic flu forecasts.





Contacts and sources:
Nicholas Reich
University of Massachusetts Amherst


Publication: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Stephen A. Lauer, Kyra H. Grantz, Qifang Bi, Forrest K. Jones, Qulu Zheng, Hannah R. Meredith, Andrew S. Azman, Nicholas G. Reich, Justin Lessler. Annals of Internal Medicine, 2020; DOI: 10.7326/M20-0504







Patients with Mild COVID-19 Infectious Up to 8 Days After Symptom Disappear Say Doctors


In a new study, researchers found that half of the patients they treated for mild COVID-19 infection still had coronavirus for up to eight days after symptoms disappeared. The research letter was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

COVID-19
Credit: NIH / National Institute of Allergy and Infectious Diseases (NIAID)

In “Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection,” Lixin Xie, MD, Lokesh Sharma, PhD, and co-authors report on a study of 16 patients with COVID-19, who were treated and released from the Treatment Center of PLA General Hospital in Beijing between January 28 and Feb. 9, 2020. Patients studied had a median age of 35.5 years.

Researchers collected samples from throat swabs taken from all patients on alternate days and analyzed. Patients were discharged after their recovery and confirmation of negative viral status by at least two consecutive polymerase chain reaction (PCR) tests.

“The most significant finding from our study is that half of the patients kept shedding the virus even after resolution of their symptoms,” said co-lead author Dr. Sharma, instructor of medicine, Section of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, Yale School of Medicine. “More severe infections may have even longer shedding times.”

The primary symptoms in these patients included fever, cough, pain in the pharynx (pharyngalgia) and difficult or labored breathing (dyspnea). Patients were treated with a range of medications.

The time from infection to onset of symptoms (incubation period) was five days among all but one patient. The average duration of symptoms was eight days, while the length of time patients remained contagious after the end of their symptoms ranged from one to eight days. Two patients had diabetes and one had tuberculosis, neither of which affected the timing of the course of COVID-19 infection.

“If you had mild respiratory symptoms from COVID-19 and were staying at home so as not to infect people, extend your quarantine for another two weeks after recovery to ensure that you don’t infect other people,” recommended corresponding author Lixin Xie, MD, professor, College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing.

The authors had a special message for the medical community: “COVID-19 patients can be infectious even after their symptomatic recovery, so treat the asymptomatic/recently recovered patients as carefully as symptomatic patients.”

The researchers emphasized that all of these patients had milder infections and recovered from the disease, and that the study looked at a small number of patients. They noted that it is unclear whether similar results would hold true for more vulnerable patients such as the elderly, those with suppressed immune systems and patients on immunosuppressive therapies.

“Further studies are needed to investigate if the real-time PCR-detected virus is capable of transmission in the later stages of COVID-19 infection,” Dr. Xie added.

This study was supported by funding from China’s 13th Five-Year National Key Grant, China Scholarship Council, Beijing Nova Program and the Beijing Nova Program Interdisciplinary Cooperation Project.
Contacts and sources:
American Thoracic Society

Publication: Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. De Chang, Guoxin Mo, Xin Yuan, Yi Tao, Xiaohua Peng, Fusheng Wang, Lixin Xie, Lokesh Sharma, Charles S Dela Cruz, Enqiang Qin. American Journal of Respiratory and Critical Care Medicine, 2020; DOI: 10.1164/rccm.202003-0524LE




Lucy Had an Ape-Like Brain



Three million year old brain imprints show that Australopithecus afarensis infants may have had a long dependence on caregivers

A new study led by paleoanthropologists Philipp Gunz and Simon Neubauer from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, reveals that Lucy’s species Australopithecus afarensis had an ape-like brain. However, the protracted brain growth suggests that – as is the case in humans – infants may have had a long dependence on caregivers.


Brain imprints in fossil skulls of the species Australopithecus afarensis (famous for “Lucy”, and the “Dikika child” from Ethiopia pictured here in frontal and lateral view) shed new light on the evolution of brain growth and organization

Credit: © Philipp Gunz, CC BY-NC-ND 4.0

The species Australopithecus afarensis inhabited East Africa more than three million years ago, and occupies a key position in the hominin family tree, as it is widely accepted to be ancestral to all later hominins, including the human lineage. “Lucy and her kind provide important evidence about early hominin behavior. They walked upright, had brains that were around 20 percent larger than those of chimpanzees, may have used sharp stone tools,” explains senior author Zeresenay Alemseged from the University of Chicago, who directs the Dikika field project in Ethiopia, where the skeleton of an Australopithecus child was found in the year 2000. “Our new results show how their brains developed, and how they were organized,” adds Alemseged.

To study brain growth and organization in Australopithecus afarensis the researchers scanned the fossil cranium of the Dikika child using synchrotron microtomography at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. With the help of this state-of the-art technology researchers can reveal the age at death with a precision of a few weeks.

In addition, seven other well-preserved fossil crania, from the Ethiopian Hadar site, were scanned using high-resolution conventional tomography. Several years of painstaking fossil reconstruction, and counting of dental growth lines, yielded an exceptionally preserved brain imprint of the Dikika child, a precise age at death, new endocranial volume estimates, and previously undetected endocranial features of well-known Australopithecus fossils.

These data shed new light on two questions that have been controversial: Is there evidence for human-like brain reorganization in Australopithecus afarensis? Was the pattern of brain growth in A. afarensis more similar to that of chimpanzees or that of humans?
Extended childhood


Brain imprints (shown in white) in fossil skulls of the species Australopithecus afarensis shed new light on the evolution of brain growth and organization. Several years of painstaking fossil reconstruction, and counting of dental growth lines, yielded an exceptionally preserved brain imprint of the Dikika child, and a precise age at death.

Credit: © Philipp Gunz, CC BY-NC-ND 4.0

Contrary to previous claims, the endocranial imprints of Australopithecus afarensis reveal an ape-like brain organization, and no features derived towards humans. However, a comparison of infant and adult endocranial volumes nevertheless indicates more human-like protracted brain growth in Australopithecus afarensis, likely critical for the evolution of a long period of childhood learning in hominins.

The brains of modern humans are not only much larger than those of our closest living ape relatives, they are also organized differently, and take longer to grow and mature. For example, compared with chimpanzees, modern human infants learn longer at the expense of being entirely dependent on parental care for longer periods of time. Together, these characteristics are important for human cognition and social behavior, but their evolutionary origins remain unclear. Brains do not fossilize, but as the brain grows and expands before and after birth, the tissues surrounding its outer layer leave an imprint in the bony braincase. Based on these endocasts the researchers could measure endocranial volume, and infer key aspects of brain organization from impressions of brain convolutions in the skull.

Differences in brain organization


Brains do not fossilize, but as the brain grows, the tissues surrounding its outer layer leave an imprint in the bony braincase. The Dikika child’s endocranial imprint reveals an ape-like brain organization, and no features derived towards humans.

Credit: © Philipp Gunz, CC BY-NC-ND 4.0

A key difference between apes and humans involves the organization of the brain’s parietal and occipital lobes. “In all ape brains, a well-defined lunate sulcus approximates the anterior boundary of the primary visual cortex of the occipital lobes,” explains co-author Dean Falk from Florida State University, a specialist in interpreting endocranial imprints. Some have previously argued that structural changes of the brain resulted in a more backwards (human-like) placement of the lunate sulcus on endocasts of australopiths, and eventually to the disappearance of a clear endocranial impression in humans. Hypothetically, such brain reorganization in australopiths could have been linked to behaviors that were more complex than those of their great ape relatives (e.g., tool manufacture, mentalizing, and vocal communication). Unfortunately, the lunate sulcus typically does not reproduce well on endocasts, so there is unresolved controversy about its position in australopiths.

The exceptionally well preserved endocast of the Dikika child has an unambiguous impression of a lunate sulcus in an ape-like position. Likewise, the computed tomographic scans reveal a previously undetected impression of an ape-like lunate sulcus in a well-known fossil of an adult Australopithecus individual from Hadar (A.L. 162-28). Contrary to previous claims, the researchers did not find evidence for brain reorganization in any Australopithecus afarensis endocast that preserves detailed sulcal impressions.
Virtual dental histology

In infants, synchrotron computed tomographic scans of the dentition make it possible to determine an individual’s age at death by counting dental growth lines. Similar to the growth rings of a tree, virtual sections of a tooth reveal incremental growth lines reflecting the body’s internal rhythm. Studying the fossilized teeth of the Dikika infant, the team’s dental experts Paul Tafforeau (ESRF), Adeline Le Cabec (ESRF/Max Planck Institute for Evolutionary Anthropology), and Tanya Smith (Griffith University) calculated an age at death of 861 days (2.4 years).

“After seven years of work, we finally had all the puzzle pieces to study the evolution of brain growth,” says lead author Philipp Gunz: “The age at death of the Dikika child and its endocranial volume, the endocranial volumes of the best-preserved adult Australopithecus afarensis fossils, and comparative data of more than 1600 modern humans and chimpanzees.”
Protracted brain growth

The pace of dental development of the Dikika infant was broadly comparable to that of chimpanzees and therefore faster than in modern humans. However, given that the brains of Australopithecus afarensis adults were roughly 20 percent larger than those of chimpanzees, the Dikika child’s small endocranial volume suggests a prolonged period of brain development relative to chimpanzees. “Even a conservative comparison of the Dikika infant to small-statured and small-brained adults like Lucy, suggests that brain growth in Australopithecus afarensis was protracted as in humans today,” explains Simon Neubauer.

“Our data show that Australopithecus afarensis had an ape-like brain organization, but suggest that these brains developed over a longer period of time than in chimpanzees,” concludes Philipp Gunz. Among primates in general, different rates of growth and maturation are associated with different infant-care strategies, suggesting that the extended period of brain growth in Australopithecus afarensis may have been linked to a long dependence on caregivers. Alternatively, slow brain growth could also primarily represent a way to spread the energetic requirements of dependent offspring over many years in environments where food is not abundant. In either case the protracted brain growth in Australopithecus afarensis provided a basis for subsequent evolution of the brain and social behavior in hominins, and was likely critical for the evolution of a long period of childhood learning.


Contacts and sources:
Dr. Philipp Gunz, Max Planck Institute for Evolutionary Anthropology, Leipzig
Sandra Jacob,  Max Planck Institute for Evolutionary Anthropology, Leipzig




Publication: Australopithecus afarensis endocasts suggest ape-like brain organization and prolonged brain growth Philipp Gunz, Simon Neubauer, Dean Falk, Paul Tafforeau, Adeline Le Cabec, Tanya M. Smith, William H. Kimbel, Fred Spoor, Zeresenay Alemseged
Science Advances, 1 April 2020, DOI: 10.1126/sciadv.aaz4729