Jul 25, 2020

An origin story for a family of oddball meteorites

Most meteorites that have landed on Earth are fragments of planetesimals, the very earliest protoplanetary bodies in the solar system. Scientists have thought that these primordial bodies either completely melted early in their history or remained as piles of unmelted rubble.

But a family of meteorites has befuddled researchers since its discovery in the 1960s. The diverse fragments, found all over the world, seem to have broken off from the same primordial body, and yet the makeup of these meteorites indicates that their parent must have been a puzzling chimera that was both melted and unmelted.

Now researchers at MIT and elsewhere have determined that the parent body of these rare meteorites was indeed a multilayered, differentiated object that likely had a liquid metallic core. This core was substantial enough to generate a magnetic field that may have been as strong as Earth's magnetic field is today.

Their results, published in the journal Science Advances, suggest that the diversity of the earliest objects in the solar system may have been more complex than scientists had assumed.

"This is one example of a planetesimal that must have had melted and unmelted layers. It encourages searches for more evidence of composite planetary structures," says lead author Clara Maurel, a graduate student in MIT's Department of Earth, Atmospheric, and Planetary Sciences (EAPS). "Understanding the full spectrum of structures, from nonmelted to fully melted, is key to deciphering how planetesimals formed in the early solar system."

Maurel's co-authors include EAPS professor Benjamin Weiss, along with collaborators at Oxford University, Cambridge University, the University of Chicago, Lawrence Berkeley National Laboratory, and the Southwest Research Institute.

Oddball irons


The solar system formed around 4.5 billion years ago as a swirl of super-hot gas and dust. As this disk gradually cooled, bits of matter collided and merged to form progressively larger bodies, such as planetesimals.

The majority of meteorites that have fallen to Earth have compositions that suggest they came from such early planetesimals that were either of two types: melted, and unmelted. Both types of objects, scientists believe, would have formed relatively quickly, in less than a few million years, early in the solar system's evolution.

If a planetesimal formed in the first 1.5 million years of the solar system, short-lived radiogenic elements could have melted the body entirely due to the heat released by their decay. Unmelted planetesimals could have formed later, when their material had lower quantities of radiogenic elements, insufficient for melting.

There has been little evidence in the meteorite record of intermediate objects with both melted and unmelted compositions, except for a rare family of meteorites called IIE irons.

"These IIE irons are oddball meteorites," Weiss says. "They show both evidence of being from primordial objects that never melted, and also evidence for coming from a body that's completely or at least substantially melted. We haven't known where to put them, and that's what made us zero in on them."

Magnetic pockets

Scientists have previously found that both melted and unmelted IIE meteorites originated from the same ancient planetesimal, which likely had a solid crust overlying a liquid mantle, like Earth. Maurel and her colleagues wondered whether the planetesimal also may have harbored a metallic, melted core.

"Did this object melt enough that material sank to the center and formed a metallic core like that of the Earth?" Maurel says. "That was the missing piece to the story of these meteorites."

The team reasoned that if the planetesimal did host a metallic core, it could very well have generated a magnetic field, similar to the way Earth's churning liquid core produces a magnetic field. Such an ancient field could have caused minerals in the planetesimal to point in the direction of the field, like a needle in a compass. Certain minerals could have kept this alignment over billions of years.

Maurel and her colleagues wondered whether they might find such minerals in samples of IIE meteorites that had crashed to Earth. They obtained two meteorites, which they analyzed for a type of iron-nickel mineral known for its exceptional magnetism-recording properties.

The team analyzed the samples using the Lawrence Berkeley National Laboratory's Advanced Light Source, which produces X-rays that interact with mineral grains at the nanometer scale, in a way that can reveal the minerals' magnetic direction.

Sure enough, the electrons within a number of grains were aligned in a similar direction -- evidence that the parent body generated a magnetic field, possibly up to several tens of microtesla, which is about the strength of Earth's magnetic field. After ruling out less plausible sources, the team concluded that the magnetic field was most likely produced by a liquid metallic core. To generate such a field, they estimate the core must have been at least several tens of kilometers wide.

Such complex planetesimals with mixed composition (both melted, in the form of a liquid core and mantle, and unmelted in the form of a solid crust), Maurel says, would likely have taken over several million years to form -- a formation period that is longer than what scientists had assumed until recently.

But where within the parent body did the meteorites come from? If the magnetic field was generated by the parent body's core, this would mean that the fragments that ultimately fell to Earth could not have come from the core itself. That's because a liquid core only generates a magnetic field while still churning and hot. Any minerals that would have recorded the ancient field must have done so outside the core, before the core itself completely cooled.

Working with collaborators at the University of Chicago, the team ran high-velocity simulations of various formation scenarios for these meteorites. They showed that it was possible for a body with a liquid core to collide with another object, and for that impact to dislodge material from the core. That material would then migrate to pockets close to the surface where the meteorites originated.

"As the body cools, the meteorites in these pockets will imprint this magnetic field in their minerals. At some point, the magnetic field will decay, but the imprint will remain," Maurel says. "Later on, this body is going to undergo a lot of other collisions until the ultimate collisions that will place these meteorites on Earth's trajectory."

Was such a complex planetesimal an outlier in the early solar system, or one of many such differentiated objects? The answer, Weiss says, may lie in the asteroid belt, a region populated with primordial remnants.

Read more at Science Daily

MRI scans of the brains of 130 mammals, including humans, indicate equal connectivity

Illustration of neurons
Researchers at Tel Aviv University, led by Prof. Yaniv Assaf of the School of Neurobiology, Biochemistry and Biophysics and the Sagol School of Neuroscience and Prof. Yossi Yovel of the School of Zoology, the Sagol School of Neuroscience, and the Steinhardt Museum of Natural History, conducted a first-of-its-kind study designed to investigate brain connectivity in 130 mammalian species. The intriguing results, contradicting widespread conjectures, revealed that brain connectivity levels are equal in all mammals, including humans.

"We discovered that brain connectivity -- namely the efficiency of information transfer through the neural network -- does not depend on either the size or structure of any specific brain," says Prof. Assaf. "In other words, the brains of all mammals, from tiny mice through humans to large bulls and dolphins, exhibit equal connectivity, and information travels with the same efficiency within them. We also found that the brain preserves this balance via a special compensation mechanism: when connectivity between the hemispheres is high, connectivity within each hemisphere is relatively low, and vice versa."

Participants included researchers from the Kimron Veterinary Institute in Beit Dagan, the School of Computer Science at TAU and the Technion's Faculty of Medicine. The paper was published in Nature Neuroscience on June 8.

"Brain connectivity is a central feature, critical to the functioning of the brain," Prof. Assaf explains. "Many scientists have assumed that connectivity in the human brain is significantly higher compared to other animals, as a possible explanation for the superior functioning of the 'human animal.'" On the other hand, according to Prof. Yovel, "We know that key features are conserved throughout the evolutionary process. Thus, for example, all mammals have four limbs. In this project we wished to explore the possibility that brain connectivity may be a key feature of this kind -- maintained in all mammals regardless of their size or brain structure. To this end we used advanced research tools."

The project began with advanced diffusion MRI scans of the brains of about 130 mammals, each representing a different species. (All of the brains were removed from dead animals, and no animals were euthanized for the purposes of this study.) The brains, obtained from the Kimron Veterinary Institute, represented a very wide range of mammals -- from tiny bats weighing 10 grams to dolphins whose weight can reach hundreds of kilograms. Since the brains of about 100 of these mammals had never been MRI-scanned before, the project generated a novel and globally unique database. The brains of 32 living humans were also scanned in the same way. The unique technology, which detects the white matter in the brain, enabled the researchers to reconstruct the neural network: the neurons and their axons (nerve fibers) through which information is transferred, and the synapses (junctions) where they meet.

The next challenge was comparing the scans of different types of animals, whose brains vary greatly in size and/or structure. For this purpose the researchers employed tools from Network Theory, a branch of mathematics that enabled them to create and apply a uniform gauge of brain conductivity: the number of synopses a message must cross to get from one location to another in the neural network.

"A mammal's brain consists of two hemispheres connected to each other by a set of neural fibers (axons) that transfer information," Prof. Assaf explains. "For every brain we scanned, we measured four connectivity gages: connectivity in each hemisphere (intrahemispheric connections), connectivity between the two hemispheres (interhemispheric), and overall connectivity. We discovered that overall brain connectivity remains the same for all mammals, large or small, including humans. In other words, information travels from one location to another through the same number of synapses. It must be said, however, that different brains use different strategies to preserve this equal measure of overall connectivity: some exhibit strong interhemispheric connectivity and weaker connectivity within the hemispheres, while others display the opposite."

Prof. Yovel describes another interesting discovery. "We found that variations in connectivity compensation characterize not only different species but also different individuals within the same species," he says. "In other words, the brains of some rats, bats, or humans exhibit higher interhemispheric connectivity at the expense of connectivity within the hemispheres, and the other way around -- compared to others of the same species. It would be fascinating to hypothesize how different types of brain connectivity may affect various cognitive functions or human capabilities such as sports, music or math. Such questions will be addressed in our future research."

Read more at Science Daily

Jul 24, 2020

How COVID-19 causes smell loss

Coronavirus illustration
Temporary loss of smell, or anosmia, is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. Studies suggest it better predicts the disease than other well-known symptoms such as fever and cough, but the underlying mechanisms for loss of smell in patients with COVID-19 have been unclear.

Now, an international team of researchers led by neuroscientists at Harvard Medical School has identified the olfactory cell types most vulnerable to infection by SARS-CoV-2, the virus that causes COVID-19.

Surprisingly, sensory neurons that detect and transmit the sense of smell to the brain are not among the vulnerable cell types.

Reporting in Science Advances on July 24, the research team found that olfactory sensory neurons do not express the gene that encodes the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. Instead, ACE2 is expressed in cells that provide metabolic and structural support to olfactory sensory neurons, as well as certain populations of stem cells and blood vessel cells.

The findings suggest that infection of nonneuronal cell types may be responsible for anosmia in COVID-19 patients and help inform efforts to better understand the progression of the disease.

"Our findings indicate that the novel coronavirus changes the sense of smell in patients not by directly infecting neurons but by affecting the function of supporting cells," said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.

This implies that in most cases, SARS-CoV-2 infection is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia, Datta added, a condition that is associated with a variety of mental and social health issues, particularly depression and anxiety.

"I think it's good news, because once the infection clears, olfactory neurons don't appear to need to be replaced or rebuilt from scratch," he said. "But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."

A majority of COVID-19 patients experience some level of anosmia, most often temporary, according to emerging data. Analyses of electronic health records indicate that COVID-19 patients are 27 times more likely to have smell loss but are only around 2.2 to 2.6 times more likely to have fever, cough or respiratory difficulty, compared to patients without COVID-19.

Some studies have hinted that anosmia in COVID-19 differs from anosmia caused by other viral infections, including by other coronaviruses.

For example, COVID-19 patients typically recover their sense of smell over the course of weeks -- much faster than the months it can take to recover from anosmia caused by a subset of viral infections known to directly damage olfactory sensory neurons. In addition, many viruses cause temporary loss of smell by triggering upper respiratory issues such as stuffy nose. Some COVID-19 patients, however, experience anosmia without any nasal obstruction.

Pinpointing vulnerability

In the current study, Datta and colleagues set out to better understand how sense of smell is altered in COVID-19 patients by pinpointing cell types most vulnerable to SARS-CoV-2 infection.

They began by analyzing existing single-cell sequencing datasets that in total catalogued the genes expressed by hundreds of thousands of individual cells in the upper nasal cavities of humans, mice and nonhuman primates.

The team focused on the gene ACE2, widely found in cells of the human respiratory tract, which encodes the main receptor protein that SARS-CoV-2 targets to gain entry into human cells. They also looked at another gene, TMPRSS2, which encodes an enzyme thought to be important for SARS-CoV-2 entry into the cell.

The analyses revealed that both ACE2 and TMPRSS2 are expressed by cells in the olfactory epithelium -- a specialized tissue in the roof of the nasal cavity responsible for odor detection that houses olfactory sensory neurons and a variety of supporting cells.

Neither gene, however, was expressed by olfactory sensory neurons. By contrast, these neurons did express genes associated with the ability of other coronaviruses to enter cells.

The researchers found that two specific cell types in the olfactory epithelium expressed ACE2 at similar levels to what has been observed in cells of the lower respiratory tract, the most common targets of SARS-CoV-2, suggesting a vulnerability to infection.

These included sustentacular cells, which wrap around sensory neurons and are thought to provide structural and metabolic support, and basal cells, which act as stem cells that regenerate the olfactory epithelium after damage. The presence of proteins encoded by both genes in these cells was confirmed by immunostaining.

In additional experiments, the researchers found that olfactory epithelium stem cells expressed ACE2 protein at higher levels after artificially induced damage, compared with resting stem cells. This may suggest additional SARS-CoV-2 vulnerability, but it remains unclear whether or how this is important to the clinical course of anosmia in patients with COVID-19, the authors said.

Datta and colleagues also analyzed gene expression in nearly 50,000 individual cells in the mouse olfactory bulb, the structure in the forebrain that receives signals from olfactory sensory neurons and is responsible for initial odor processing.

Neurons in the olfactory bulb did not express ACE2. The gene and associated protein were present only in blood vessel cells, particularly pericytes, which are involved in blood pressure regulation, blood-brain barrier maintenance and inflammatory responses. No cell types in the olfactory bulb expressed the TMPRSS2 gene.

Smell loss clue

Together, these data suggest that COVID-19-related anosmia may arise from a temporary loss of function of supporting cells in the olfactory epithelium, which indirectly causes changes to olfactory sensory neurons, the authors said.

"We don't fully understand what those changes are yet, however," Datta said. "Sustentacular cells have largely been ignored, and it looks like we need to pay attention to them, similar to how we have a growing appreciation of the critical role that glial cells play in the brain."

The findings also offer intriguing clues into COVID-19-associated neurological issues. The observations are consistent with hypotheses that SARS-CoV-2 does not directly infect neurons but may instead interfere with brain function by affecting vascular cells in the nervous system, the authors said. This requires further investigation to verify, they added.

The study results now help accelerate efforts to better understand smell loss in patients with COVID-19, which could in turn lead to treatments for anosmia and the development of improved smell-based diagnostics for the disease.

"Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it's persistent," Datta said. "It can have serious psychological consequences and could be a major public health problem if we have a growing population with permanent loss of smell."

The team also hope the data can help pave inroads for questions on disease progression such as whether the nose acts as a reservoir for SARS-CoV-2. Such efforts will require studies in facilities that allow experiments with live coronavirus and analyses of human autopsy data, the authors said, which are still difficult to come by. However, the collaborative spirit of pandemic-era scientific research calls for optimism.

"We initiated this work because my lab had a couple of datasets ready to analyze when the pandemic hit, and we published an initial preprint," Datta said. "What happened after that was amazing, researchers across the globe offered to share and merge their data with us in a kind of impromptu global consortium. This was a real collaborative achievement."

Read more at Science Daily

COVID-19 lockdown caused 50 percent global reduction in human-linked Earth vibrations

Seismograph
The lack of human activity during lockdown caused human-linked vibrations in the Earth to drop by an average of 50% between March and May 2020.

This quiet period, likely caused by the total global effect of social distancing measures, closure of services and industry, and drops in tourism and travel, is the longest and most pronounced quiet period of seismic noise in recorded history.

The new research, led by the Royal Observatory of Belgium and five other institutions around the world including Imperial College London, showed that the dampening of 'seismic noise' caused by humans was more pronounced in more densely populated areas.

The relative quietness allowed researchers to listen in to previously concealed earthquake signals, and could help us differentiate between human and natural seismic noise more clearly than ever before.

Co-author Dr Stephen Hicks, from Imperial's Department of Earth Science and Engineering, said: "This quiet period is likely the longest and largest dampening of human-caused seismic noise since we started monitoring the Earth in detail using vast monitoring networks of seismometers.

"Our study uniquely highlights just how much human activities impact the solid Earth, and could let us see more clearly than ever what differentiates human and natural noise."

The paper is published today in Science.

Anthropause

Measured by instruments called seismometers, seismic noise is caused by vibrations within the Earth, which travel like waves. The waves can be triggered by earthquakes, volcanoes, and bombs -- but also by daily human activity like travel and industry.

Although 2020 has not seen a reduction in earthquakes, the drop in human-caused seismic noise is unprecedented. The strongest drops were found in urban areas, but the study also found signatures of the lockdown on sensors buried hundreds of metres underground and in more remote areas.

Human-generated noise usually dampens during quiet periods like over the Christmas/New Year period and Chinese New Year, and during weekends and overnight. However, the drop in vibrations caused by COVID-19 lockdown measures eclipse even those seen during these periods.

Some researchers are dubbing this drop in anthropogenic (human-caused) noise and pollution the 'anthropause'.

Dr Hicks said: "This is the first global study of the impact of the coronavirus anthropause on the solid Earth beneath our feet."

To gather the data, researchers looked at seismic data from a global network of 268 seismic stations in 117 countries and found significant noise reductions compared to before any lockdown at 185 of those stations. Beginning in China in late January 2020, and followed by Europe and the rest of the world in March to April 2020, researchers tracked the 'wave' of quietening between March and May as worldwide lockdown measures took hold.

The largest drops in vibrations were seen in the most densely populated areas, like Singapore and New York City, but drops were also seen in remote areas like Germany's Black Forest and Rundu in Namibia. Citizen-owned seismometers, which tend to measure more localised noise, noted large drops around universities and schools around Cornwall, UK and Boston, USA -- a drop in noise 20 per cent larger than seen during school holidays. Countries like Barbados, where lockdown coincided with the tourist season, saw a 50 per cent decrease in noise. This coincided with flight data that suggested tourists returned home in the weeks before official lockdown.

Listening in

Over the past few decades, seismic noise has gradually increased as economies and populations have grown.

The drastic changes to daily life caused by the pandemic have provided a unique opportunity to study their environmental impacts, such as reductions in emissions and pollution in the atmosphere. The changes have also given us the opportunity to listen in to the Earth's natural vibrations without the distortions of human input.

The study reports the first evidence that previously concealed earthquake signals, especially during daytime, appeared much clearer on seismometers in urban areas during lockdown.

The researchers say the lockdown quietening could also help them differentiate between human-caused noise and natural signals that might warn of upcoming natural disasters.

Lead author Dr Thomas Lecocq from the Royal Observatory of Belgium said: "With increasing urbanisation and growing global populations, more people will be living in geologically hazardous areas. It will therefore become more important than ever to differentiate between natural and human-caused noise so that we can 'listen in' and better monitor the ground movements beneath our feet. This study could help to kick-start this new field of study."

The study's authors hope that their work will spawn further research on the seismic lockdown, as well as finding previously hidden signals from earthquakes and volcanoes.

Read more at Science Daily

Vikings had smallpox and may have helped spread the world's deadliest virus

Viking ship
Scientists have discovered extinct strains of smallpox in the teeth of Viking skeletons -- proving for the first time that the killer disease plagued humanity for at least 1400 years.

Smallpox spread from person to person via infectious droplets, killed around a third of sufferers and left another third permanently scarred or blind. Around 300 million people died from it in the 20th century alone before it was officially eradicated in 1980 through a global vaccination effort -- the first human disease to be wiped out.

Now an international team of scientists have sequenced the genomes of newly discovered strains of the virus after it was extracted from the teeth of Viking skeletons from sites across northern Europe. The findings have been published in Science today (July 23, 2020).

Professor Eske Willerslev, of St John's College, University of Cambridge, and director of The Lundbeck Foundation GeoGenetics Centre, University of Copenhagen, led the study.

He said: "We discovered new strains of smallpox in the teeth of Viking skeletons and found their genetic structure is different to the modern smallpox virus eradicated in the 20th century. We already knew Vikings were moving around Europe and beyond, and we now know they had smallpox. People travelling around the world quickly spread Covid-19 and it is likely Vikings spread smallpox. Just back then, they travelled by ship rather than by plane.

"The 1400-year-old genetic information extracted from these skeletons is hugely significant because it teaches us about the evolutionary history of the variola virus that caused smallpox."

Smallpox was eradicated throughout most of Europe and the United States by the beginning of the 20th century but remained endemic throughout Africa, Asia, and South America. The World Health Organisation launched an eradication programme in 1967 that included contact tracing and mass communication campaigns -- all public health techniques that countries have been using to control today's coronavirus pandemic. But it was the global roll out of a vaccine that ultimately enabled scientists to stop smallpox in its tracks.

Historians believe smallpox may have existed since 10,000 BC but until now there was no scientific proof that the virus was present before the 17th century. It is not known how it first infected humans but, like Covid-19, it is believed to have come from animals.

Professor Martin Sikora, one of the senior authors leading the study, from the Centre for GeoGenetics, University of Copenhagen, said: "The timeline of the emergence of smallpox has always been unclear but by sequencing the earliest-known strain of the killer virus, we have proved for the first time that smallpox existed during the Viking Age.

"While we don't know for sure if these strains of smallpox were fatal and caused the death of the Vikings we sampled, they certainly died with smallpox in their bloodstream for us to be able to detect it up to 1400 years later. It is also highly probable there were epidemics earlier than our findings that scientists have yet to discover DNA evidence of."

The team of researchers found smallpox -- caused by the variola virus -- in 11 Viking-era burial sites in Denmark, Norway, Russia, and the UK. They also found it in multiple human remains from Öland, an island off the east coast of Sweden with a long history of trade. The team were able to reconstruct near-complete variola virus genomes for four of the samples.

Dr Lasse Vinner, one of the first authors and a virologist from The Lundbeck Foundation GeoGenetics Centre, said: "Understanding the genetic structure of this virus will potentially help virologists understand the evolution of this and other viruses and add to the bank of knowledge that helps scientists fight emerging viral diseases.

"The early version of smallpox was genetically closer in the pox family tree to animal poxviruses such as camelpox and taterapox, from gerbils. It does not exactly resemble modern smallpox which show that virus evolved. We don't know how the disease manifested itself in the Viking Age -- it may have been different from those of the virulent modern strain which killed and disfigured hundreds of millions."

Dr Terry Jones, one of the senior authors leading the study, a computational biologist based at the Institute of Virology at Charité -- Universitätsmedizin Berlin and the Centre for Pathogen Evolution at the University of Cambridge, said: "There are many mysteries around poxviruses. To find smallpox so genetically different in Vikings is truly remarkable. No one expected that these smallpox strains existed. It has long been believed that smallpox was in Western and Southern Europe regularly by 600 AD, around the beginning of our samples.

"We have proved that smallpox was also widespread in Northern Europe. Returning crusaders or other later events have been thought to have first brought smallpox to Europe, but such theories cannot be correct. While written accounts of disease are often ambiguous, our findings push the date of the confirmed existence of smallpox back by a thousand years."

Dr Barbara Mühlemann, one of the first authors and a computational biologist, took part in the research during her PhD at the Centre for Pathogen Evolution at the University of Cambridge, and is now also based at the Institute of Virology at Charité, said: "The ancient strains of smallpox have a very different pattern of active and inactive genes compared to the modern virus. There are multiple ways viruses may diverge and mutate into milder or more dangerous strains. This is a significant insight into the steps the variola virus took in the course of its evolution."

Dr Jones added: "Knowledge from the past can protect us in the present. When an animal or plant goes extinct, it isn't coming back. But mutations can re-occur or revert and viruses can mutate or spill over from the animal reservoir so there will always be another zoonosis."

Zoonosis refers to an infectious disease outbreak caused by a pathogen jumping from a non-human animal to a human.

The research is part of a long-term project sequencing 5000 ancient human genomes and their associated pathogens made possible thanks to a scientific collaboration between The Lundbeck Foundation, The Wellcome Trust, The Nordic Foundation, and Illumina Inc.

Read more at Science Daily

Neanderthals may have had a lower threshold for pain

Depiction of early humans, photo concept
Pain is mediated through specialized nerve cells that are activated when potentially harmful things affect various parts of our bodies. These nerve cells have a special ion channel that has a key role in starting the electrical impulse that signals pain and is sent to the brain. According to a new study, people who inherited the Neanderthal variant of this ion channel experience more pain.

As several Neanderthal genomes of high quality are now available researchers can identify genetic changes that were present in many or all Neanderthals, investigate their physiological effects and look into their consequences when they occur in people today. Looking into one gene that carries such changes, Hugo Zeberg, Svante Pääbo and colleagues found that some people, especially from central and south America but also in Europe, have inherited a Neanderthal variant of a gene that encodes an ion channel that initiates the sensation of pain.

By using data from a huge population study in the UK, the authors show that people in the UK who carry the Neanderthal variant of the ion channel experience more pain. "The biggest factor for how much pain people report is their age. But carrying the Neanderthal variant of the ion channel makes you experience more pain similar to if you were eight years older," says lead author Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology and Karolinska Institutet. "The Neanderthal variant of the ion channel carries three amino acid differences to the common, 'modern' variant," explains Zeberg. "While single amino acid substitutions do not affect the function of the ion channel, the full Neanderthal variant carrying three amino acid substitutions leads to heightened pain sensitivity in present-day people."

On a molecular level, the Neanderthal ion channel is more easily activated which may explain why people who inherited it have a lowered pain threshold. "Whether Neanderthals experienced more pain is difficult to say because pain is also modulated both in the spinal cord and in the brain," says Pääbo. "But this work shows that their threshold for initiating pain impulses was lower than in most present-day humans."

From Science Daily

Jul 23, 2020

Flood data from 500 years: Rivers and climate change in Europe

Overflowing rivers can cause enormous problems: Worldwide, the annual damage caused by river floods is estimated at over 100 billion dollars -- and it continues to rise. To date it has been unclear whether Europe is currently in a flood-rich period from a long-term perspective.

Austrian flood expert Prof. Günter Blöschl from TU Wien (Vienna) has led a large international study involving a total of 34 research groups that provides clear evidence that the past three decades were among the most flood-rich periods in Europe during the past 500 years, and that this period differs from others in terms of its extent, air temperatures and flood seasonality. Compared to the past, floods tend to be larger in many places, the timing has shifted and the relationship between flood occurrence and air temperatures has reversed. In the past, floods tended to occur more frequently in cold phases, while today, global warming is one of the main drivers of their increase. The results of the study have now been published in "Nature" magazine.

Historical data from half a millennium

"From our previous research, we already knew how climate change has affected Europe's floods in the past 50 years," says Alberto Viglione from the Politecnico di Torino, one of the key authors of the publication. "For forecasts of the next decades, however, it is also important to understand whether this is a completely new situation or whether this is just a repetition of something that has already occurred. So far, the available data had not been sufficient to ascertain whether this is the case or not. We have examined this question in great detail and can now say with confidence: Yes, flooding characteristics in recent decades are unlike those of the previous centuries."

For the study, tens of thousands of historical documents containing contemporary flood reports from the period 1500 to 2016 were analysed. The TU Wien team has worked with historians from all over Europe. "The particular challenge of this study consisted in making the very different texts of the different centuries and different cultural regions comparable," explains Andrea Kiss from the Vienna University of Technology, researcher and historian herself, and one of the key authors of the publication. "We managed to achieve this comparability by putting all the texts in their respective historical contexts with painstaking attention to detail."

Formerly cold, now warm: River floods now function differently

The data analysis identified nine flood-rich periods and associated regions. Among the most notable periods were 1560-1580 (western and central Europe), 1760-1800 (most of Europe), 1840-1870 (western and southern Europe) and 1990-2016 (western and central Europe). Comparisons with air temperature reconstructions showed that these historical flood periods were substantially cooler than intervening phases.

"This finding seems to contradict the observation that, in some areas such as in the northwest of Europe, the recent warmer climate is aligned with larger floods," says Günter Blöschl. "Our study shows for the first time that the underlying mechanisms have changed: While, in the past, floods have occurred more frequently under colder conditions, the opposite is the case now. The hydrological conditions of the present are very different from those in the past."

The timing of the floods within the year has also changed. Previously, 41% of Central European floods occurred in the summer, compared to 55% today. These shifts are related to changes in precipitation, evaporation and snowmelt and are an important indicator for distinguishing the role of climate change from that of other controls such as deforestation and river management.

These findings have been made possible by a new data base compiled by the study authors that includes the exact dating of almost all flood events reported by written sources. So far, one had to often rely on other, less precise sources of information, such as lake sediments. It is the first study worldwide to evaluate historical flood periods for an entire continent in such detail.

Read more at Science Daily

Genomic basis of bat superpowers revealed: Like how they survive deadly viruses

The genetic material that codes for bat adaptations and superpowers -- such as the ability to fly, to use sound to move effortlessly in complete darkness, to tolerate and survive potentially deadly viruses, and to resist aging and cancer -- has been revealed and published in Nature. Liliana M. Dávalos, a Stony Brook University evolutionary biologist and co-author, worked as part of the executive committee of the global consortium of scientists, Bat1K, to sequence the genome of six widely divergent living bat species.

Although other bat genomes have been published before, the Bat1K genomes are 10 times more complete than any bat genome published to date.

One aspect of the paper findings shows evolution through gene expansion and loss in a family of genes, APOBEC3, which is known to play an important role in immunity to viruses in other mammals. The details in the paper that explain this evolution set the groundwork for investigating how these genetic changes, found in bats but not in other mammals, could help prevent the worst outcomes of viral diseases in other mammals, including humans.

"More and more, we find gene duplications and losses as important processes in the evolution of new features and functions across the Tree of Life. But, determining when genes have duplicated is difficult if the genome is incomplete, and it is even harder to figure out if genes have been lost. At extremely high quality, the new bat genomes leave no doubts about changes in important gene families that could not be discovered otherwise with lower-quality genomes," said Dávalos, a Professor in Department of Ecology and Evolution in the College of Arts and Sciences at Stony Brook University.

To generate the bat genomes, the team used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource in Dresden, Germany to sequence the bat's DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present. While previous efforts had identified genes with the potential to influence the unique biology of bats, uncovering how gene duplications contributed to this unique biology was complicated by incomplete genomes.

The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Fereuungulata that consists of carnivorans (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).

To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats' unique traits.

"It is thanks to a series of sophisticated statistical analyses that we have started to uncover the genetics behind bats' 'superpowers,' including their strong apparent abilities to tolerate and overcome RNA viruses," said Dávalos.

The researchers found evidence the exquisite genomes revealed "fossilized viruses," evidence of surviving past viral infections, and showed that bat genomes contained a higher diversity of these viral remnants than other species providing a genomic record of ancient historical interaction with viral infections. The genomes also revealed the signatures of many other genetic elements besides ancient viral insertions, including 'jumping genes' or transposable elements.

Read more at Science Daily

First ever image of a multi-planet system around a sun-like star captured by ESO telescope

The European Southern Observatory's Very Large Telescope (ESO's VLT) has taken the first ever image of a young, Sun-like star accompanied by two giant exoplanets. Images of systems with multiple exoplanets are extremely rare, and -- until now -- astronomers had never directly observed more than one planet orbiting a star similar to the Sun. The observations can help astronomers understand how planets formed and evolved around our own Sun.

Just a few weeks ago, ESO revealed a planetary system being born in a new, stunning VLT image. Now, the same telescope, using the same instrument, has taken the first direct image of a planetary system around a star like our Sun, located about 300 light-years away and known as TYC 8998-760-1.

"This discovery is a snapshot of an environment that is very similar to our Solar System, but at a much earlier stage of its evolution," says Alexander Bohn, a PhD student at Leiden University in the Netherlands, who led the new research published today in the Astrophysical Journal Letters.

"Even though astronomers have indirectly detected thousands of planets in our galaxy, only a tiny fraction of these exoplanets have been directly imaged," says co-author Matthew Kenworthy, Associate Professor at Leiden University, adding that "direct observations are important in the search for environments that can support life." The direct imaging of two or more exoplanets around the same star is even more rare; only two such systems have been directly observed so far, both around stars markedly different from our Sun. The new ESO's VLT image is the first direct image of more than one exoplanet around a Sun-like star. ESO's VLT was also the first telescope to directly image an exoplanet, back in 2004, when it captured a speck of light around a brown dwarf, a type of 'failed' star.

"Our team has now been able to take the first image of two gas giant companions that are orbiting a young, solar analogue," says Maddalena Reggiani, a postdoctoral researcher from KU Leuven, Belgium, who also participated in the study. The two planets can be seen in the new image as two bright points of light distant from their parent star, which is located in the upper left of the frame (click on the image to view the full frame). By taking different images at different times, the team were able to distinguish these planets from the background stars.

The two gas giants orbit their host star at distances of 160 and about 320 times the Earth-Sun distance. This places these planets much further away from their star than Jupiter or Saturn, also two gas giants, are from the Sun; they lie at only 5 and 10 times the Earth-Sun distance, respectively. The team also found the two exoplanets are much heavier than the ones in our Solar System, the inner planet having 14 times Jupiter's mass and the outer one six times.

Bohn's team imaged this system during their search for young, giant planets around stars like our Sun but far younger. The star TYC 8998-760-1 is just 17 million years old and located in the Southern constellation of Musca (The Fly). Bohn describes it as a "very young version of our own Sun."

These images were possible thanks to the high performance of the SPHERE instrument on ESO's VLT in the Chilean Atacama desert. SPHERE blocks the bright light from the star using a device called coronagraph, allowing the much fainter planets to be seen. While older planets, such as those in our Solar System, are too cool to be found with this technique, young planets are hotter, and so glow brighter in infrared light. By taking several images over the past year, as well as using older data going back to 2017, the research team have confirmed that the two planets are part of the star's system.

Read more at Science Daily

New role for white blood cells in the developing brain

Whether white blood cells can be found in the brain has been controversial, and their role there a complete mystery. In a study published in Cell, an international team of scientists led by Professor Adrian Liston (Babraham Institute, UK & VIB-KU Leuven, Belgium) describe a population of specialised brain-resident immune cells discovered in the mouse and human brain, and show that the presence of white blood cells is essential for normal brain development in mice.

Like a highly fortified headquarters, our brain enjoys special protection from what is circulating in the rest of our body through the blood-brain barrier. This highly selective border makes sure that passage from the blood to the brain is tightly regulated.

The blood-brain barrier also separates the brain from our body's immune system, which is why it has its own resident immune cells, called microglia, which trigger inflammation and tissue repair. Microglia arrive in the brain during embryonic development, and later on, the population becomes self-renewing.

Yet, white blood cells -- which are part of our immune system -- have been found to play a role in different brain diseases, including multiple sclerosis, Alzheimer's and Parkinson's disease or stroke. Whether or not white blood cells can be found in healthy brains as well, and what they might be doing there, has been subject of intense debate. An interdisciplinary team of scientists led by Prof. Adrian Liston (Babraham Institute and VIB-KU Leuven) set out to find the answers.

White blood cells in the brain

"A misconception about white blood cells comes from their name," explains Dr Oliver Burton (Babraham Institute). "These 'immune cells' are not just present in the blood. They are constantly circulating around our body and enter all of our organs, including -- as it turns out -- the brain. We are only just starting to discover what white blood cells do when they leave the blood. This research indicates that they act as a go-between, transferring information from the rest of the body to the brain environment"

The team quantified and characterised a small but distinct population of brain-resident T helper cells present in mouse and human brain tissue. T cells are a specific type of white blood cells specialized for scanning cell surfaces for evidence of infection and triggering an appropriate immune response. New technologies allowed the researchers to study the cells in great detail, including the processes by which circulating T cells entered the brain and began to develop the features of brain-resident T cells.

Dr Carlos Roca (Babraham Institute): "Science is becoming increasingly multidisciplinary. Here, we didn't just bring in expertise from immunology, neuroscience and microbiology, but also from computer science and applied mathematics. New approaches for data analysis allow us to reach a much deeper level of understanding of the biology of the white blood cells we found in the brain."

An evolutionary role

When T helper cells are absent from the brain, the scientists found that the resident immune cells -- microglia -- in the mouse brain remained suspended between a fetal and adult developmental state. Observationally, mice lacking brain T cells showed multiple changes in their behavior. The analysis points to an important role for brain-resident T cells in brain development. If T cells participate in normal brain development in mice, could the same be true in humans?

"In mice, the wave of entry of immune cells at birth triggers a switch in brain development," says Liston. "Humans have a much longer gestation than mice though, and we don't know about the timing of immune cell entry into the brain. Does this occur before birth? Is it delayed until after birth? Did a change in timing of entry contribute to the evolution of enhanced cognitive capacity in humans?"

The findings open up a whole new range of questions about how the brain and our immune system interact. "It has been really exciting to work on this project. We are learning so much about how our immune system can alter our brain, and how our brain modifies our immune system. The two are far more interconnected than we previously thought," says Dr Emanuela Pasciuto (VIB-KU Leuven).

The study also brings in a connection with the gut microbiome, says Liston: "There are now multiple links between the bacteria in our gut and different neurological conditions, but without any convincing explanations for what connects them. We show that white blood cells are modified by gut bacteria, and then take that information with them into the brain. This could be the route by which our gut microbiome influences the brain."

Read more at Science Daily

Jul 22, 2020

'Lost' world's rediscovery is step towards finding habitable planets

The rediscovery of a lost planet could pave the way for the detection of a world within the habitable 'Goldilocks zone' in a distant solar system.

The planet, the size and mass of Saturn with an orbit of thirty-five days, is among hundreds of 'lost' worlds that University of Warwick astronomers are pioneering a new method to track down and characterise in the hope of finding cooler planets like those in our solar system, and even potentially habitable planets.

Reported in Astrophysical Journal Letters, the planet named NGTS-11b orbits a star 620 light years away and is located five times closer to its sun than Earth is to our own.

The planet was originally found in a search for planets in 2018 by the Warwick-led team using data from NASA's TESS telescope. This uses the transit method to spot planets, scanning for the telltale dip in light from the star that indicates that an object has passed between the telescope and the star. However, TESS only scans most sections of the sky for 27 days. This means many of the longer period planets only transit once in the TESS data. And without a second observation the planet is effectively lost. The University of Warwick led team followed up one of these 'lost' planets using the telescopes at the Next-Generation Transit Survey (NGTS) in Chile and observed the star for seventy-nine nights, eventually catching the planet transiting for a second time nearly a year after the first detected transit.

Dr Samuel Gill from the Department of Physics at the University of Warwick said: "By chasing that second transit down we've found a longer period planet. It's the first of hopefully many such finds pushing to longer periods.

"These discoveries are rare but important, since they allow us to find longer period planets than other astronomers are finding. Longer period planets are cooler, more like the planets in our own Solar System.

"NGTS-11b has a temperature of only 160°C -- cooler than Mercury and Venus. Although this is still too hot to support life as we know it, it is closer to the Goldilocks zone than many previously discovered planets which typically have temperatures above 1000°C."

The Goldilocks zone refers to a range of orbits that would allow a planet or moon to support liquid water: too close to its star and it will be too hot, but too far away and it will be too cold.

Co-author Dr Daniel Bayliss from the University of Warwick said: "This planet is out at a thirty-five days orbit, which is a much longer period than we usually find them. It is exciting to see the Goldilocks zone within our sights."

Co-author Professor Pete Wheatley from the University of Warwick said: "The original transit appeared just once in the TESS data, and it was our team's painstaking detective work that allowed us to find it again a year later with NGTS.

"NGTS has twelve state-of-the-art telescopes, which means that we can monitor multiple stars for months on end, searching for lost planets. The dip in light from the transit is only 1% deep and occurs only once every 35 days, putting it out of reach of other telescopes. "

Read more at Science Daily

New cosmic magnetic field structures discovered in galaxy NGC 4217

Spiral galaxies such as our Milky Way can have sprawling magnetic fields. There are various theories about their formation, but so far the process is not well understood. An international research team has now analysed the magnetic field of the Milky Way-like galaxy NGC 4217 in detail on the basis of radio astronomical observations and has discovered as yet unknown magnetic field structures. The data suggest that star formation and star explosions, so-called supernovae, are responsible for the visible structures.

The team led by Dr. Yelena Stein from Ruhr-Universität Bochum, the Centre de Données astronomiques de Strasbourg and the Max Planck Institute for Radio Astronomy in Bonn together with US-American and Canadian colleagues, published their report in the journal Astronomy and Astrophysics, released online on 21 July 2020.

The analysed data had been compiled in the project "Continuum Halos in Nearby Galaxies," where radio waves were utilised to measure 35 galaxies. "Galaxy NGC 4217 is of particular interest to us," explains Yelena Stein, who began the study at the Chair of Astronomy at Ruhr-Universität Bochum under Professor Ralf-Jürgen Dettmar and who currently works at the Centre de Données astronomiques de Strasbourg. NGC 4217 is similar to the Milky Way and is only about 67 million light years away, which means relatively close to it, in the Ursa Major constellation. The researchers therefore hope to successfully transfer some of their findings to our home galaxy.

Magnetic fields and origins of star formation

When evaluating the data from NGC 4217, the researchers found several remarkable structures. The galaxy has an X-shaped magnetic field structure, which has also been observed in other galaxies, extending far outwards from the galaxy disk, namely over 20,000 light years.

In addition to the X-shape, the team found a helix structure and two large bubble structures, also called superbubbles. The latter originate from places where many massive stars explode as supernovae, but also where stars are formed that emit stellar winds in the process. Researchers therefore suspect a connection between these phenomena.

"It is fascinating that we discover unexpected phenomena in every galaxy whenever we use radio polarisation measurements," points out Dr. Rainer Beck from the MPI for Radio Astronomy in Bonn, one of the authors of the study. "Here in NGC 4217, it is huge magnetic gas bubbles and a helix magnetic field that spirals upwards into the galaxy's halo."

The analysis moreover revealed large loop structures in the magnetic fields along the entire galaxy. "This has never been observed before," explains Yelena Stein. "We suspect that the structures are caused by star formation, because at these points matter is ejected outward."

Read more at Science Daily

Even if you want to, you can't ignore how people look or sound

Your perceptions of someone you just met are influenced in part by what they look like and how they sound.

But can you ignore how someone looks or how they sound if you're told it is not relevant?

Probably not, at least in most cases, a new Ohio State University study found.

For example, some study participants were shown a photo of a face and heard a brief snippet of speech at the same time and were told that the photo and voice belonged to different people.

In some cases, participants were told to rate how strong an accent they thought the person shown in the photo would have.

Participants thought the person in the photo would have a more accented voice if the words they heard also had a stronger accent -- despite being told the image and sound represented two different people.

"Even though we told them to ignore the voice, they couldn't do it completely," said study author Kathryn Campbell-Kibler, an associate professor of linguistics at Ohio State.

"Some of the information from the voice seeped into their evaluation of the face."

The same was true when participants were asked to evaluate how "good-looking" the person with a particular voice was -- they were influenced by the photo they viewed, even when told it was a different person from the speaker they heard.

Although study participants usually could not ignore the irrelevant information, there was one intriguing exception in which participants feared showing a racial stereotype when it came to gauging accented voices.

The study was published online this week in the Journal of Sociolinguistics.

The study included 1,034 people who visited an exhibit hosted by Ohio State's Department of Linguistics at the Center of Science and Industry, a science museum in Columbus.

Participants were shown photos of 15 men on a television screen. As each photo was shown, they heard a single-word recording repeated three times over the course of five seconds, also by one of 15 men. Depending on what group they were in, participants had to rate how accented or good-looking the face or the voice was.

Some of the speakers these study participants heard had been rated by people in a previous study as sounding relatively unaccented. Other voices were from people who had learned English at older ages and had been rated as having more of an accent.

When participants evaluated the combined face and voice and were not told to ignore anything, they evaluated "good-looking" mostly based on the face, and "accented" on the voice -- as expected.

But some people were told to evaluate the face while ignoring the voice, or evaluate the voice while ignoring the face, because they represented two different people.

In those cases, some people evaluated the face on the "good-looking" dimension and some evaluated the face on the "accented" dimension. The same was true for evaluating the voice. In both cases, they had to ignore the other input, voice or face.

"We found that people could exercise some control over what information to favor, the voice or the face, depending on what we told them to do," Campbell-Kibler said.

"But in most cases, they were unable to entirely eliminate the irrelevant information."

There was one exception: People were able to completely ignore the face when rating how accented the voice sounded.

Campbell-Kibler said the reason seems to be that the participants, most of whom were white, were being careful not to show any racial stereotyping.

"Some of the participants explicitly told us they were attempting to avoid responses that could be seen as stereotypical," she said.

They knew that how a person looks has no real connection to how they sound, even though racial stereotypes often prompt people to associate strong accents with people who don't look white.

"They sensed a danger is showing racial bias when it came to evaluating accents. That's why they were careful to exclude what the face looked like when evaluating if the voice sounded accented," Campbell-Kibler said.

"They didn't have that issue when evaluating 'good-looking,' because that is seen as subjective enough that you can't really be wrong," Campbell-Kibler said.

Because this study used photographs rather than video, the audio people heard had a stronger influence on them than it might in real life, she said. Videos would probably have a stronger effect on people's evaluations than these still images.

But the main message is the same: We are influenced by all the information we have available, whether it is applicable or not.

Read more at Science Daily

Autopsies reveal surprising cardiac changes in COVID-19 patients

A series of autopsies conducted by LSU Health New Orleans pathologists shows the damage to the hearts of COVID-19 patients is not the expected typical inflammation of the heart muscle associated with myocarditis, but rather a unique pattern of cell death in scattered individual heart muscle cells. They report the findings of a detailed study of hearts from 22 deaths confirmed due to COVID-19 in a Research Letter published in Circulation, available here.

"We identified key gross and microscopic changes that challenge the notion that typical myocarditis is present in severe SARS-CoV-2 infection," says Richard Vander Heide, M.D., Ph.D., Professor and Director of Pathology Research at LSU Health New Orleans School of Medicine. "While the mechanism of cardiac injury in COVID-19 is unknown, we propose several theories that bear further investigation that will lead to greater understanding and potential treatment interventions."

The team of LSU Health pathologists led by Dr. Vander Heide, an experienced cardiovascular pathologist, also found that unlike the first SARS coronavirus, SARS-CoV-2 was not present in heart muscle cells. Nor were there occluding blood clots in the coronary arteries.

Their previously reported results revealed diffuse alveolar damage (DAD) -- damage to the small airspaces of the lung where gas exchange occurs -- along with blood clots and bleeding in the small blood vessels and capillaries of the lung, were the major contributors to death.

"These findings, along with severely enlarged right ventricles, may indicate extreme stress on the heart secondary to acute pulmonary disease," adds Sharon Fox, MD, PhD, Associate Director of Research and Development in the Department of Pathology at LSU Health New Orleans School of Medicine.

The autopsies, believed to be some of the first reported from the US, were conducted on 22 patients who died of COVID-19 at University Medical Center in New Orleans. The majority were African American. The ten male and twelve female patients ranged in age from 44-79. Although there were other underlying conditions, the majority had high blood pressure, half had insulin-treated type 2 diabetes, and about 41% had obesity.

The LSU Health New Orleans pathologists, as have others, also found viral infection of some of the cells in the lining of the smaller blood vessels (endothelium). Although at low levels, it may be enough to cause dysfunction leading to individual cell death. The effects of the so-called "cytokine storm" (severe overreaction of the immune system cells fighting the infection) associated with COVID may also play a role.

"Given that inflammatory cells can pass through the heart without being present in the tissue proper, a role for cytokine-induced endothelial damage cannot be ruled out," says Dr. Vander Heide.

Read more at Science Daily

Jul 21, 2020

Chinese phase 2 trial finds COVID-19 vaccine is safe and induces an immune response

A phase 2 trial of an Ad5 vectored COVID-19 vaccine candidate, conducted in China, has found that the vaccine is safe and induces an immune response, according to new research published in The Lancet.

The randomised trial sought to evaluate the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May 2020. The results provide data from a wider group of participants than their phase 1 trial, including a small sub-group of participants aged over 55 years and older, and will inform phase 3 trials of the vaccine.

However, the authors note that it is important to stress that no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against SARS-CoV-2 infection.

Professor Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, China, says: "The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway."

Currently, there are about 250 candidate vaccines against SARS-CoV-2 in development worldwide, including mRNA vaccines, replicating or non-replicating viral vectored vaccines, DNA vaccines, autologous dendritic cell-based vaccine and inactive virus vaccines. At least 17 of them are currently under evaluation in clinical trials.

The vaccine in this trial uses a weakened human common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.

508 participants took part in the trial of the new vaccine. Of these, 253 received a high dose of the vaccine (at 1×1011 viral particles/1.0mL), 129 received a low dose (at 5×1010 viral particles/1.0mL) and 126 received placebo. Approximately two thirds of participants (309; 61%) were aged in 18-44 years, a quarter (134; 26%) were aged 45-54 years, and 13% (65) were 55 years or older.

Participants were monitored for immediate adverse reactions for 30 minutes after injection and were followed for any injection-site or systemic adverse reactions within 14- and 28-days post-vaccination. Serious adverse events reported by participants during the whole study period were documented. Blood samples were taken from participants immediately before the vaccination and 14- and 28-days post-vaccination to measure antibody responses.

The trial found that 95% (241/253) of participants in the high dose group and 91% (118/129) of the recipients in the low dose group showed either T cell or antibody immune responses at day 28 post-vaccination.

The vaccine induced a neutralising antibody response in 59% (148/253) and 47% (61/129) of participants, and binding antibody response in 96% (244/253) and 97% (125/129) of participants, in the high and low dose groups, respectively, by day 28. The participants in the placebo group showed no antibody increase from baseline.

Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with geometric mean titres of 19.5, and 18.3 in participants receiving the high and low dose, respectively. The binding antibody response peaked at 656.5 ELISA units and 571 ELISA units for the high and low dose of the vaccine, respectively.

T cell responses were also found in 90% (227/253) and 88% (113/129) of participants receiving the vaccine at high and low dose, respectively. A median of 11 spot-forming cells and 10 spot-forming cells per 1 × 10? peripheral blood mononuclear cells in participants in the high dose and low dose groups, respectively, were observed at day 28.

The proportions of participants who had any adverse reactions such as fever, fatigue and injection-site pain were significantly higher in vaccine recipients than those in placebo recipients (72% [183/253] in the high dose group, 74% [96/129] in the low dose group, 37% [46/126] in the placebo group). However, most adverse reactions were mild or moderate. Within 28 days, 24 (9%) participants in the high dose group had severe (grade 3) adverse reactions, which was significantly higher than in those receiving the low dose or placebo (one (1%) participant in the low dose group, and 2 people (2%) in the placebo group). The most common severe reaction was fever.

The authors note that pre-existing immunity to the human adenovirus which was used as the vector (ie, the Ad5 vector) for this vaccine and increasing age could partially hamper the specific immune responses to vaccination, particularly for the antibody responses. Among the 508 participants, 266 (52%) participants showed a high pre-existing immunity to Ad5 vector, while 242 (48%) had low pre-existing immunity to Ad5 vector. Those with a higher pre-existing anti-Ad5 immunity showed an inferior immune response (the binding and neutralising antibody levels were around two times larger in people with low pre-existing anti-Ad5 immunity, compared to those with high pre-existing immunity). Compared with the younger population, older participants generally had significantly lower immune responses and higher tolerability to the Ad5 vectored COVID-19 vaccine.

Professor Wei Chen, Beijing Institute of Biotechnology, China, says: "Since elderly individuals face a high risk of serious illness and even death associated with COVID-19 infection, they are an important target population for a COVID-19 vaccine. It is possible that an additional dose may be needed in order to induce a stronger immune response in the elderly population, but further research is underway to evaluate this."

The authors note that the trial was conducted in Wuhan, China, and the baseline immunity is representative of Chinese adults at that time, but other countries may have different rates of immunity which should be considered. Additionally, the trial only followed participants for 28 days and no data about the durability of the vaccine-induced immunity is available from this study. Importantly, no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine the efficacy of the candidate vaccine or any immunological risk associated with antibody induced by vaccination when having a virus exposure.

Read more at Science Daily

The hair-raising reason for goosebumps

Goosebumps, concept photo
If you've ever wondered why we get goosebumps, you're in good company -- so did Charles Darwin, who mused about them in his writings on evolution. Goosebumps might protect animals with thick fur from the cold, but we humans don't seem to benefit from the reaction much -- so why has it been preserved during evolution all this time?

In a new study, Harvard University scientists have discovered the reason: the cell types that cause goosebumps are also important for regulating the stem cells that regenerate the hair follicle and hair. Underneath the skin, the muscle that contracts to create goosebumps is necessary to bridge the sympathetic nerve's connection to hair follicle stem cells. The sympathetic nerve reacts to cold by contracting the muscle and causing goosebumps in the short term, and by driving hair follicle stem cell activation and new hair growth over the long term.

Published in the journal Cell, these findings in mice give researchers a better understanding of how different cell types interact to link stem cell activity with changes in the outside environment.

"We have always been interested in understanding how stem cell behaviors are regulated by external stimuli. The skin is a fascinating system: it has multiple stem cells surrounded by diverse cell types, and is located at the interface between our body and the outside world. Therefore, its stem cells could potentially respond to a diverse array of stimuli -- from the niche, the whole body, or even the outside environment," said Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology, who led the study in collaboration with Professor Sung-Jan Lin of National Taiwan University. "In this study, we identify an interesting dual-component niche that not only regulates the stem cells under steady state, but also modulates stem cell behaviors according to temperature changes outside."

A system for regulating hair growth

Many organs are made of three types of tissue: epithelium, mesenchyme, and nerve. In the skin, these three lineages are organized in a special arrangement. The sympathetic nerve, part of our nervous system that controls body homeostasis and our responses to external stimuli, connects with a tiny smooth muscle in the mesenchyme. This smooth muscle in turn connects to hair follicle stem cells, a type of epithelial stem cell critical for regenerating the hair follicle as well as repairing wounds.

The connection between the sympathetic nerve and the muscle has been well known, since they are the cellular basis behind goosebumps: the cold triggers sympathetic neurons to send a nerve signal, and the muscle reacts by contracting and causing the hair to stand on end. However, when examining the skin under extremely high resolution using electron microscopy, the researchers found that the sympathetic nerve not only associated with the muscle, but also formed a direct connection to the hair follicle stem cells. In fact, the nerve fibers wrapped around the hair follicle stem cells like a ribbon.

"We could really see at an ultrastructure level how the nerve and the stem cell interact. Neurons tend to regulate excitable cells, like other neurons or muscle with synapses. But we were surprised to find that they form similar synapse-like structures with an epithelial stem cell, which is not a very typical target for neurons," Hsu said.

Next, the researchers confirmed that the nerve indeed targeted the stem cells. The sympathetic nervous system is normally activated at a constant low level to maintain body homeostasis, and the researchers found that this low level of nerve activity maintained the stem cells in a poised state ready for regeneration. Under prolonged cold, the nerve was activated at a much higher level and more neurotransmitters were released, causing the stem cells to activate quickly, regenerate the hair follicle, and grow new hair.

The researchers also investigated what maintained the nerve connections to the hair follicle stem cells. When they removed the muscle connected to the hair follicle, the sympathetic nerve retracted and the nerve connection to the hair follicle stem cells was lost, showing that the muscle was a necessary structural support to bridge the sympathetic nerve to the hair follicle.

How the system develops

In addition to studying the hair follicle in its fully formed state, the researchers investigated how the system initially develops -- how the muscle and nerve reach the hair follicle in the first place.

"We discovered that the signal comes from the developing hair follicle itself. It secretes a protein that regulates the formation of the smooth muscle, which then attracts the sympathetic nerve. Then in the adult, the interaction turns around, with the nerve and muscle together regulating the hair follicle stem cells to regenerate the new hair follicle. It's closing the whole circle -- the developing hair follicle is establishing its own niche," said Yulia Shwartz, a postdoctoral fellow in the Hsu lab. She was a co-first author of the study, along with Meryem Gonzalez-Celeiro, a graduate student in the Hsu Lab, and Chih-Lung Chen, a postdoctoral fellow in the Lin lab.

Responding to the environment

With these experiments, the researchers identified a two-component system that regulates hair follicle stem cells. The nerve is the signaling component that activates the stem cells through neurotransmitters, while the muscle is the structural component that allows the nerve fibers to directly connect with hair follicle stem cells.

"You can regulate hair follicle stem cells in so many different ways, and they are wonderful models to study tissue regeneration," Shwartz said. "This particular reaction is helpful for coupling tissue regeneration with changes in the outside world, such as temperature. It's a two-layer response: goosebumps are a quick way to provide some sort of relief in the short term. But when the cold lasts, this becomes a nice mechanism for the stem cells to know it's maybe time to regenerate new hair coat."

In the future, the researchers will further explore how the external environment might influence the stem cells in the skin, both under homeostasis and in repair situations such as wound healing.

"We live in a constantly changing environment. Since the skin is always in contact with the outside world, it gives us a chance to study what mechanisms stem cells in our body use to integrate tissue production with changing demands, which is essential for organisms to thrive in this dynamic world," Hsu said.

Read more at Science Daily

Scientists discover volcanoes on Venus are still active

Surface of Venus illustration
A new study identified 37 recently active volcanic structures on Venus. The study provides some of the best evidence yet that Venus is still a geologically active planet. A research paper on the work, which was conducted by researchers at the University of Maryland and the Institute of Geophysics at ETH Zurich, Switzerland, was published in the journal Nature Geoscience on July 20, 2020.

"This is the first time we are able to point to specific structures and say 'Look, this is not an ancient volcano but one that is active today, dormant perhaps, but not dead,'" said Laurent Montési, a professor of geology at UMD and co-author of the research paper. "This study significantly changes the view of Venus from a mostly inactive planet to one whose interior is still churning and can feed many active volcanoes."

Scientists have known for some time that Venus has a younger surface than planets like Mars and Mercury, which have cold interiors. Evidence of a warm interior and geologic activity dots the surface of the planet in the form of ring-like structures known as coronae, which form when plumes of hot material deep inside the planet rise through the mantle layer and crust. This is similar to the way mantle plumes formed the volcanic Hawaiian Islands.

But it was thought that the coronae on Venus were probably signs of ancient activity, and that Venus had cooled enough to slow geological activity in the planet's interior and harden the crust so much that any warm material from deep inside would not be able to puncture through. In addition, the exact processes by which mantle plumes formed coronae on Venus and the reasons for variation among coronae have been matters for debate.

In the new study, the researchers used numerical models of thermo-mechanic activity beneath the surface of Venus to create high-resolution, 3D simulations of coronae formation. Their simulations provide a more detailed view of the process than ever before.

The results helped Montési and his colleagues identify features that are present only in recently active coronae. The team was then able to match those features to those observed on the surface of Venus, revealing that some of the variation in coronae across the planet represents different stages of geological development. The study provides the first evidence that coronae on Venus are still evolving, indicating that the interior of the planet is still churning.

"The improved degree of realism in these models over previous studies makes it possible to identify several stages in corona evolution and define diagnostic geological features present only at currently active coronae," Montési said. "We are able to tell that at least 37 coronae have been very recently active."

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Plato was right: Earth is made, on average, of cubes

Statue of Plato
Plato, the Greek philosopher who lived in the 5th century B.C.E., believed that the universe was made of five types of matter: earth, air, fire, water, and cosmos. Each was described with a particular geometry, a platonic shape. For earth, that shape was the cube.

Science has steadily moved beyond Plato's conjectures, looking instead to the atom as the building block of the universe. Yet Plato seems to have been onto something, researchers have found.

In a new paper in the Proceedings of the National Academy of Sciences, a team from the University of Pennsylvania, Budapest University of Technology and Economics, and University of Debrecen uses math, geology, and physics to demonstrate that the average shape of rocks on Earth is a cube.

"Plato is widely recognized as the first person to develop the concept of an atom, the idea that matter is composed of some indivisible component at the smallest scale," says Douglas Jerolmack, a geophysicist in Penn's School of Arts & Sciences' Department of Earth and Environmental Science and the School of Engineering and Applied Science's Department of Mechanical Engineering and Applied Mechanics. "But that understanding was only conceptual; nothing about our modern understanding of atoms derives from what Plato told us.

"The interesting thing here is that what we find with rock, or earth, is that there is more than a conceptual lineage back to Plato. It turns out that Plato's conception about the element earth being made up of cubes is, literally, the statistical average model for real earth. And that is just mind-blowing."

The group's finding began with geometric models developed by mathematician Gábor Domokos of the Budapest University of Technology and Economics, whose work predicted that natural rocks would fragment into cubic shapes.

"This paper is the result of three years of serious thinking and work, but it comes back to one core idea," says Domokos. "If you take a three-dimensional polyhedral shape, slice it randomly into two fragments and then slice these fragments again and again, you get a vast number of different polyhedral shapes. But in an average sense, the resulting shape of the fragments is a cube."

Domokos pulled two Hungarian theoretical physicists into the loop: Ferenc Kun, an expert on fragmentation, and János Török, an expert on statistical and computational models. After discussing the potential of the discovery, Jerolmack says, the Hungarian researchers took their finding to Jerolmack to work together on the geophysical questions; in other words, "How does nature let this happen?"

"When we took this to Doug, he said, 'This is either a mistake, or this is big,'" Domokos recalls. "We worked backward to understand the physics that results in these shapes."

Fundamentally, the question they answered is what shapes are created when rocks break into pieces. Remarkably, they found that the core mathematical conjecture unites geological processes not only on Earth but around the solar system as well.

"Fragmentation is this ubiquitous process that is grinding down planetary materials," Jerolmack says. "The solar system is littered with ice and rocks that are ceaselessly smashing apart. This work gives us a signature of that process that we've never seen before."

Part of this understanding is that the components that break out of a formerly solid object must fit together without any gaps, like a dropped dish on the verge of breaking. As it turns out, the only one of the so-called platonic forms -- polyhedra with sides of equal length -- that fit together without gaps are cubes.

"One thing we've speculated in our group is that, quite possibly Plato looked at a rock outcrop and after processing or analyzing the image subconsciously in his mind, he conjectured that the average shape is something like a cube," Jerolmack says.

"Plato was very sensitive to geometry," Domokos adds. According to lore, the phrase "Let no one ignorant of geometry enter" was engraved at the door to Plato's Academy. "His intuitions, backed by his broad thinking about science, may have led him to this idea about cubes," says Domokos.

To test whether their mathematical models held true in nature, the team measured a wide variety of rocks, hundreds that they collected and thousands more from previously collected datasets. No matter whether the rocks had naturally weathered from a large outcropping or been dynamited out by humans, the team found a good fit to the cubic average.

However, special rock formations exist that appear to break the cubic "rule." The Giant's Causeway in Northern Ireland, with its soaring vertical columns, is one example, formed by the unusual process of cooling basalt. These formations, though rare, are still encompassed by the team's mathematical conception of fragmentation; they are just explained by out-of-the-ordinary processes at work.

"The world is a messy place," says Jerolmack. "Nine times out of 10, if a rock gets pulled apart or squeezed or sheared -- and usually these forces are happening together -- you end up with fragments which are, on average, cubic shapes. It's only if you have a very special stress condition that you get something else. The earth just doesn't do this often."

The researchers also explored fragmentation in two dimensions, or on thin surfaces that function as two-dimensional shapes, with a depth that is significantly smaller than the width and length. There, the fracture patterns are different, though the central concept of splitting polygons and arriving at predictable average shapes still holds.

"It turns out in two dimensions you're about equally likely to get either a rectangle or a hexagon in nature," Jerolmack says. "They're not true hexagons, but they're the statistical equivalent in a geometric sense. You can think of it like paint cracking; a force is acting to pull the paint apart equally from different sides, creating a hexagonal shape when it cracks."

In nature, examples of these two-dimensional fracture patterns can be found in ice sheets, drying mud, or even the earth's crust, the depth of which is far outstripped by its lateral extent, allowing it to function as a de facto two-dimensional material. It was previously known that the earth's crust fractured in this way, but the group's observations support the idea that the fragmentation pattern results from plate tectonics.

Identifying these patterns in rock may help in predicting phenomenon such as rock fall hazards or the likelihood and location of fluid flows, such as oil or water, in rocks.

For the researchers, finding what appears to be a fundamental rule of nature emerging from millennia-old insights has been an intense but satisfying experience.

"There are a lot of sand grains, pebbles, and asteroids out there, and all of them evolve by chipping in a universal manner," says Domokos, who is also co-inventor of the Gömböc, the first known convex shape with the minimal number -- just two -- of static balance points. Chipping by collisions gradually eliminates balance points, but shapes stop short of becoming a Gömböc; the latter appears as an unattainable end point of this natural process.

The current result shows that the starting point may be a similarly iconic geometric shape: the cube with its 26 balance points. "The fact that pure geometry provides these brackets for a ubiquitous natural process, gives me happiness," he says.

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Jul 20, 2020

Archaeologists use tooth enamel protein to show sex of human remains

A new method for estimating the biological sex of human remains based on reading protein sequences rather than DNA has been used to study an archaeological site in Northern California. The protein-based technique gave superior results to DNA analysis in studying 55 sets of human remains between 300 and 2,300 years old. The work is published July 17 in Scientific Reports.

The method targets amelogenin, a protein found in tooth enamel, said first author Tammy Buonasera, postdoctoral researcher working with Glendon Parker, adjunct associate professor in the Department of Environmental Toxicology at the University of California, Davis. The technique was developed in Parker's laboratory.

Buonasera, Parker, Jelmer Eerkens, professor of anthropology, and colleagues compared three methods for sex determination: the new proteomic method; DNA analysis; and osteology, or analysis of the size, shape and composition of the bones themselves. They applied these methods to remains from two ancestral Ohlone villages near Sunol, California. The site is being excavated by the Far West Anthropological Research Group of Davis in collaboration with the Muwekma Ohlone tribe.

Amelogenin is a protein found in tooth enamel, the hardest and most durable substance in the human body. The gene for amelogenin happens to be located on both the X and Y sex chromosomes, and the amelogenin-Y protein is slightly different from amelogenin-X.

The method works by retrieving a tiny amount of protein from a tooth. All proteins are made up of a chain of amino acids, so the protein is analyzed to give the amino acid sequence, which then defines the protein. Each of the 20 naturally occurring amino acids is specified by a three-letter code in DNA, so it is possible to work backward from the amino acid sequence and figure out the likely DNA code.

Superior to existing methods

The researchers were able to determine the sex of all of the remains using the new protein method and all but five using DNA methods. Results from osteology and proteomics agreed in almost all cases, although examining bones themselves was only effective for about half the skeletons.

The protein method allowed them to estimate sex for children, which is not possible from osteology. It was reliable even when the signal from DNA was weak.

"This is a more sensitive technique for older skeletons where we would expect more DNA degradation," Parker said.

Being able to determine the biological sex of human remains provides a greater window into the persona of each individual. Anthropologists are interested in determining biological sex because sex interacts with health and can have a large impact on how people form an identity and are treated within a society, Eerkens said.

"Almost every human society around the world incorporates sex and gender as a way to classify people, and these can affect your status and who you associate with in society," Eerkens said. While gender and biological sex are not the same thing, they are linked, so the ability to estimate sex gives archaeologists important insight when attempting to understand the cultural aspects of gender, which are not as readily preserved.

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A new idea on how Earth's outer shell first broke into tectonic plates

The activity of the solid Earth -- for example, volcanoes in Java, earthquakes in Japan, etc -- is well understood within the context of the ~50-year-old theory of plate tectonics. This theory posits that Earth's outer shell (Earth's "lithosphere") is subdivided into plates that move relative to each other, concentrating most activity along the boundaries between plates. It may be surprising, then, that the scientific community has no firm concept on how plate tectonics got started. This month, a new answer has been put forward by Dr. Alexander Webb of the Division of Earth and Planetary Science & Laboratory for Space Research at the University of Hong Kong, in collaboration with an international team in a paper published in Nature Communications. Webb serves as corresponding author on the new work.

Dr. Webb and his team proposed that early Earth's shell heated up, which caused expansion that generated cracks. These cracks grew and coalesced into a global network, subdividing early Earth's shell into plates. They illustrated this idea via a series of numerical simulations, using a fracture mechanics code developed by the paper's first author, Professor Chunan Tang of the Dalian University of Technology. Each simulation tracks the stress and deformation experienced by a thermally-expanding shell. The shells can generally withstand about 1 km of thermal expansion (Earth's radius is ~6371 km), but additional expansion leads to fracture initiation and the rapid establishment of the global fracture network.

Although this new model is simple enough -- Earth's early shell warmed up, expanded, and cracked -- superficially this model resembles long-discredited ideas and contrasts with basic physical precepts of Earth science. Before the plate tectonic revolution of the 1960's, Earth's activities and the distribution of oceans and continents were explained by a variety of hypotheses, including the so-called expanding Earth hypothesis. Luminaries such as Charles Darwin posited that major earthquakes, mountain-building, and the distribution of land-masses were thought to result from the expansion of the Earth. However, because Earth's major internal heat source is radioactivity, and the continuous decay of radioactive elements means that there is less available heat as time moves forward, thermal expansion might be considered far less likely than its opposite: thermal contraction. Why, then, do Dr. Webb and his colleagues think that early Earth's lithosphere experienced thermal expansion?

"The answer lies in consideration of major heat-loss mechanisms that could have occurred during Earth's early periods," said Dr. Webb. "If volcanic advection, carrying hot material from depth to the surface, was the major mode of early heat-loss, that changes everything." Dominance of volcanism would have an unexpectedly chilling effect on the Earth's outer shell, as documented in Dr. Webb and co-author Dr. William Moore's earlier work (published in Nature in 2013). This is because new hot volcanic material taken from Earth's depths would have been deposited as cold material at the surface -- the heat would be lost to space. The evacuation at depth and piling up at the surface would have eventually required that the surface material sank, bringing cold material downwards. This continual downward motion of cold surface material would have had a chilling effect on the early lithosphere. Because Earth was cooling overall, the heat production and corresponding volcanism would have slowed down. Correspondingly, the downwards motion of lithosphere would have slowed with time, and thus even as the overall planet cooled, the chilled lithosphere would have been increasingly warmed via conduction from hot deep material below. This warming would have been the source of the thermal expansion invoked in the new model. The new modeling illustrates that if Earth's solid lithosphere is sufficiently thermally expanded, it would fracture, and the rapid growth of a fracture network would divide the Earth's lithosphere into plates.

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