Culture

Fossil secret may shed light on the diversity of Earth's first animals

image: Drs. Minter and Bath Enright, of the University of Portsmouth's School of the Environment, Geography and Geosciences, studied the Burgess Shale area of British Columbia, both on location in the field and with laboratory experiments.

Image: 
Dr. Orla Bath Enright

A large group of iconic fossils widely believed to shed light on the origins of many of Earth's animals and the communities they lived in may be hiding a secret.

Scientists, led by two from the University of Portsmouth, UK, are the first to model how exceptionally well preserved fossils that record the largest and most intense burst of evolution ever seen could have been moved by mudflows.

The finding, published in Communications Earth & Environment, offers a cautionary note on how palaeontologists build a picture from the remains of the creatures they study.

Until now, it has been widely accepted the fossils buried in mudflows in the Burgess Shale in Canada that show the result of the Cambrian explosion 505 million years ago had all lived together but that's now in doubt.

The Cambrian explosion was responsible for kick-starting the huge diversity of animal life now seen on the planet.

Now, Dr Nic Minter and Dr Orla Bath Enright have found that some of the animals which became fossils could have remained well preserved even after being carried large distances, throwing doubt on the idea the creatures all lived together.

Dr Minter said: "This finding might surprise scientists or lead to them striking a more cautionary tone in how they interpret early marine ecosystems from half a billion years ago.

"It has been assumed that because the Burgess Shale fossils are so well preserved, they couldn't have been transported over large distances. However, this new research shows that the general type of flow responsible for the deposits in which they were buried does not cause further damage to deceased animals. This means the fossils found in individual layers of sediment, and assumed to represent animal communities, could actually have been living far apart in distance."

Drs Minter and Bath Enright, of the University of Portsmouth's School of the Environment, Geography and Geosciences, studied the Burgess Shale area of British Columbia, both on location in the field and with laboratory experiments.

The site is an area rich in fossils entombed in the deposits of mudflows and is one of the world's most important fossil sites, with more than 65,000 specimens already collected and, so far, more than 120 species counted.

The Burgess Shale area has been fundamental to scientists in understanding the origins of animal groups and the communities they lived among and has been closely studied multiple times.

The researchers, together with collaborators from the Universities of Southampton and Saskatchewan in Canada, used fieldwork to identify how the mudflows would have behaved, and then used flume tank laboratory tests to mimic the mudflows and are confident that the bodies of certain creatures could have been moved over tens of kilometres without damage, creating the illusion of animal communities which never existed.

The Burgess Shale was discovered in the early 1900s and led to the idea of the 'Cambrian explosion' of life, with the appearance of animals representing almost all the modern phyla, and inspiring copious research and discoveries.

Dr Bath Enright said: "Many would argue that it is fundamental, even ground zero for scientists in understanding the diversity of life."

It's not known precisely what caused the mudflows which buried and moved the animals which became fossilised, but the area was subject to multiple flows, causing well preserved fossils to be found at many different levels in the shale.

"We don't know over what kind of overall time frame these many flows happened, but we know each one produced an 'event bed' that we see today stacked up on top of one another. These flows could pick up animals from multiple places as they moved across the seafloor and then dropped them all together in one place," said Dr Bath Enright.

"When we see multiple species accumulated together it can give the illusion we are seeing a single community. But we argue that an individual 'event bed' could be the product of several communities of animals being picked up from multiple places by a mudflow and then deposited together to give what looks like a much more complicated single community of animals.

"Palaeontologists need to appreciate the nature of the sediments that fossils are preserved within and what the implications of that are. We could be overestimating the complexity of early marine animal communities and therefore the patterns and drivers of evolution that have led to our present day diversity and complexity."

The researchers hope to do further study to investigate whether differences in the species that are present in other fossil sites are due to evolutionary changes through time or the nature of the flows and the effects of transport and preservation of the fossils.

Credit: 
University of Portsmouth

Synthetic SPECIES developed for use as a confinable gene drive

image: UC San Diego scientists have modified the genome of fruit flies using CRISPR-based technologies to create eight reproductively isolated species. In the future, this technique can be adapted to other organisms including plants, insects and vertebrates to provide new biocontrol opportunities.

Image: 
Akbari lab, UC San Diego

CRISPR-based technologies offer enormous potential to benefit human health and safety, from disease eradication to fortified food supplies. As one example, CRISPR-based gene drives, which are engineered to spread specific traits through targeted populations, are being developed to stop the transmission of devastating diseases such as malaria and dengue fever.

But many scientists and ethicists have raised concerns over the unchecked spread of gene drives. Once deployed in the wild, how can scientists prevent gene drives from uncontrollably spreading across populations like wildfire?

Now, scientists at the University of California San Diego and their colleagues have developed a gene drive with a built-in genetic barrier that is designed to keep the drive under control. Led by molecular geneticist Omar Akbari's lab, the researchers engineered synthetic fly species that, upon release in sufficient numbers, act as gene drives that can spread locally and be reversed if desired.

The scientists describe their SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species) development as a proof-of-concept innovation that could be portable to other species such as insect disease vectors. Spreading gene drives that limit pests that feast on valuable food crops is another example of a potential SPECIES application.

"Gene drives can potentially spread beyond intended borders and be hard to control. SPECIES offers a way to control populations in a very safe and reversible manner," said Akbari, a UC San Diego Division of Biological Sciences associate professor and senior author of the paper, which is published in the journal Nature Communications.

The idea behind the creation of SPECIES is reflective of the formation of new species in nature. As members of a single species separate over time, due to, for example, a new land formation, earthquake separation or other geological event, a new species eventually can evolve from the physical disconnection. If the new species eventually returns to mate with the original species, they could produce unviable offspring due to biological changes following the separation through a natural phenomenon known as reproductive isolation.

Working in the fly species Drosophila melanogaster, UC San Diego researchers and their colleagues at the California Institute of Technology, UC Berkeley and the Innovative Genomics Institute used CRISPR genetic-editing technologies to develop flies encoding SPECIES systems that are reproductively incompatible with wild versions of D. melanogaster.

"Even though speciation happens consistently in nature, creating a new artificial species is actually a pretty big bioengineering challenge," said Anna Buchman, the lead author of the paper. "The beauty of the SPECIES approach is that it simplifies the process, giving us a defined set of tools we need in any organism to elegantly bring about speciation."

Conceptually, when SPECIES are deployed in the wild in sufficient numbers, they can controllably drive through a population and replace all of their wild counterparts as they spread. Using malaria as an example, SPECIES mosquitoes could be developed with a genetic element that makes them incapable of transmitting malaria.

"You can spread an anti-malaria SPECIES into a target population in a confinable and controllable way," said Akbari. "Since SPECIES are incompatible with wild-type mosquitoes, their populations can be controlled and reversed by limiting their threshold population below 50 percent. This gives you the ability to confine and reverse its spread if desired."

As the SPECIES barrier completes its role in temporarily replacing wildtype populations, their numbers can be reduced with the reintroduction of wild type populations.

"This essentially allows us to harness all of the power of gene drives--like disease elimination or crop protection--without the high risk of uncontrollable spread," said Akbari.

Credit: 
University of California - San Diego

Atmospheric metal layers appear with surprising regularity

image: The word "LIDAR" was created using a flashlight.

Image: 
Zhibin Yu/CIRES, CU Boulder, Harbin Institute of Technology.

Twice a day, at dusk and just before dawn, a faint layer of sodium and other metals begins sinking down through the atmosphere, about 90 miles high above the city of Boulder, Colorado. The movement was captured by one of the world's most sensitive "lidar" instruments and reported today in the AGU journal Geophysical Research Letters.

The metals in those layers come originally from rocky material blasting into Earth's atmosphere from space, and the regularly appearing layers promise to help researchers understand better how earth's atmosphere interacts with space, even potentially how those interactions help support life.

"This is an important discovery because we have never seen these dusk/dawn features before, and because these metal layers affect many things. The metals can fall into the ocean and act as fertilizer for ecosystems, the ionized metals can affect GPS radio signals," said Xinzhao Chu, CIRES Fellow, CU Boulder professor of Aerospace Engineering Sciences, and lead author of the new assessment.

It is the first time that the metal layers--which are not harmful to people--have been seen so regularly at these extreme heights in the atmosphere. Such high-altitude metal layers were discovered by Chu's group just 10 years ago above McMurdo, Antarctica, but there they occur more sporadically. Above Boulder, they're consistent, daily, and synched with winds that occur high in the atmosphere.

"Consistent daily patterns seen in our Boulder observations tell us that there are unknown processes at play, a golden opportunity for atmospheric scientists," said Jackson Jandreau who worked alongside Chu and Yingfei Chen in this study. Chen and Jandreau are both PhD students in Chu's group.

The discovery also gives researchers a window into a crucial part of the atmosphere that is challenging to observe. It's a complicated region where interactions between the sun, earth and our planet's magnetic field can end up creating the environmental conditions in which surface life can thrive, protected from the harsh space environment.

"There are metals in the atmospheres of other planetary bodies, such as Mars, and researchers look for Earth-like features on exoplanets as indicators for hospitable environments," Chu said. "Can these metal layers be one of these features?"

Credit: 
University of Colorado at Boulder

Target protein identified for improving heart attack treatment

image: From left to right, study authors Yuening Liu, Peng Xia, Zhaokang Cheng, and Jingrui Chen and graduate student Joshua Gallo. Their work to uncover the mechanisms by which heart muscle cells die after heart attack treatment could someday lead to new treatment strategies to increase the survival and lifespan of heart attack victims.

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Photo by Cori Kogan, WSU Health Sciences Spokane

A new study led by researchers at Washington State University has identified a protein that could be the key to improving treatment outcomes after a heart attack.

Published in the Journal of Biological Chemistry, the research suggests that protein kinase A (PKA) plays a role in heart muscle cell necrosis, a major type of cell death that commonly occurs after reperfusion therapy, the treatment used to unblock arteries and restore blood flow after a heart attack.

"Our study has found that turning off a gene that controls this protein activity increased necrotic cell death and led to more heart injury and worse heart function following heart attack in a rodent model," said study author Zhaokang Cheng, an assistant professor in the WSU College of Pharmacy and Pharmaceutical Sciences. "With further research, this discovery could ultimately lead to the development of a small-molecule drug that could intervene in that pathway to limit or prevent heart muscle cell death after reperfusion therapy."

Such a drug could help reduce heart injury and increase the survival and lifespan of heart attack victims, Cheng said. Every year, about 800,000 people in the U.S. have a heart attack, which amounts to one heart attack occurring every 40 seconds.

Reperfusion therapy, which uses clot-dissolving drugs or mechanical means to unblock clogged arteries, has long been the most effective treatment for heart attack. Though it significantly reduces heart damage, patients treated with this therapy still experience some damage, about half of which actually results from the treatment itself. This is because the rapid restoration of blood flow into oxygen-deprived heart tissues can lead to a swift rise in free radicals. When left unchecked, this surge of free radicals induces oxidative stress, which can cause heart muscle cell death and heart injury as part of a condition known as ischemia/reperfusion injury.

Though scientists have long considered necrosis to be a passive, unavoidable form of cell death, recent studies have suggested that some forms of it happen in a highly regulated manner that could potentially be targeted for treatment. Little has been known about how this type of cell death is regulated, however, which is what prompted Cheng to take a closer look.

He and his team had previously screened more than 20,000 genes to look for ones that appeared to either suppress or promote necrotic cell death. One gene that stood out to them as warranting further study was PRKAR1A, which helps regulate PKA activity by encoding a protein known as PKA regulatory subunit R1alpha.

So the researchers conducted a series of experiments to validate whether the R1alpha protein can regulate necrotic cell death in a rodent model. They found that turning off the PRKAR1A gene increased cell death, both in cultured cells and in mice. Mice lacking the gene also had more heart injury and worse heart function after heart attack, as compared to wild-type mice.

Cheng explained that, under normal circumstances, the rapid increase of free radicals after heart attack treatment triggers the heart to launch its antioxidant defense system, the built-in protective mechanism that helps keep free radicals in check. What their new study findings suggest is that the antioxidant defense system cannot be launched as effectively when the R1alpha protein is removed from the heart, resulting in more oxidative stress, which leads to cell death and heart injury.

He explained that the R1alpha protein binds to another type of protein known as PKA catalytic subunits to keep PKA activity in check. When R1alpha is removed, the catalytic subunits are uncontrolled and PKA activity increases, which Cheng believes is what prevents the activation of the antioxidant defense system. This suggests that use of a small-molecule compound that selectively inhibits PKA activity could potentially block necrotic cell death and lead to better outcomes after heart attack treatment.

Though Cheng said he hoped their research would eventually allow them to test such a compound in an animal model, the next step they are pursuing is to determine whether there are other mechanisms by which PKA regulates necrotic cell death aside from the antioxidant defense system.

Credit: 
Washington State University

Antibiotics no help for mysterious lung-scarring disease, large trial finds

image: Imre Noth, MD, the chief of UVA Health's Division of Pulmonary and Critical Care Medicine, says the large study of idiopathic pulmonary fibrosis will still benefit efforts to battle the lung-scarring disease.

Image: 
UVA Health

Doctors have hoped that antibiotics could benefit patients with chronic lung diseases, but a new study has found no benefit for patients with life-threatening idiopathic pulmonary fibrosis in preventing hospitalization or death.

While there were no statistical benefits for patients with the lung-scarring disease, the new research will prevent unnecessary antibiotic use that could contribute to the growing problem of antibiotic resistance. The nationwide clinical trial - believed to be the largest idiopathic pulmonary fibrosis trial ever conducted - also collected biological samples that will advance the understanding and treatment of the mysterious and ultimately fatal illness.

"We were certainly disappointed in the results. But we remain hopeful that in further downstream analyses, we may yet find groups of patients that were potentially benefiting. In the meantime, this study will make sure that no one takes antibiotics without need," said researcher Imre Noth, MD, the chief of UVA Health's Division of Pulmonary and Critical Care Medicine. "We did view the study as great success as an NIH [National Institutes of Health] initiative, in that the pragmatic design, without blinding patients to treatment, led to rapid enrollment, ahead of schedule and basically ahead of budget, showing that large studies can be accomplished in this uncommon disease."

About Idiopathic Pulmonary Fibrosis

In idiopathic pulmonary fibrosis, scar tissue builds up in the lungs over time, preventing them from supplying adequate oxygen to the body. It typically affects people over age 50, mostly men. Patients typically survive only two to five years after diagnosis, though some live much longer.

Doctors are uncertain what triggers idiopathic pulmonary fibrosis. ("Idiopathic" means "unknown cause.") However, environmental and genetic factors may play a part, as may lung infections.

Doctors also suspect that changes in the microorganisms that naturally live in our lungs may be a factor. Scientists have increasingly come to appreciate the importance of the tiny organisms that live in our bodies and on our skin. In idiopathic pulmonary fibrosis, the thinking goes, the natural state of the microorganisms in the lungs may become unbalanced - perhaps there are too many of one type or a general loss of variety. Lab work in mice has suggested that antimicrobials may be able to help fix the problem.

To see if antimicrobial treatments could benefit idiopathic pulmonary fibrosis, researchers at 35 sites around the country conducted a randomized clinical trial with volunteers age 40 or older. A total of 513 patients enrolled between August 2017 and June 2019. Half received antimicrobial drugs, choosing between co-trimoxazol or doxycycline, while the other half received the standard care.

After a median follow-up time of 12.7 months, there was no statistically significant benefit from the antimicrobials. The time to both breathing-related hospitalization or death was unchanged.

The findings echoed those of a previous study, and the researchers say the results show that treatment with antibiotics is ineffective and unwarranted as a general treatment for idiopathic pulmonary fibrosis. They do not rule out, however, that it may be useful in a limited number of patients with known disruptions to their lung microorganisms.

"As the largest single study in IPF ever conducted, I think we are going to learn a lot as we look at things more closely. Might our choice of antibiotics have been the right ones? Were there some patients that did better than others? Who should we be targeting for treatment? All things this study will help in the future," said Noth, a top expert on the disease. "I am heartened and hopeful moving forward as this study teaches us a lot for the next one, and each study gets us closer to better treatments and a cure."

Credit: 
University of Virginia Health System

New study explores link between economic shock and physical inactivity

(Carlisle, Pa.) -- A new study published in the American Journal of Lifestyle Medicine finds critical links between job loss and physical inactivity in young adults during the U.S. Great Recession of 2008-09 that can be crucial to understanding the role of adverse economic shocks on physical activity during the COVID-19 pandemic. It is the first study to examine how job losses during the Great Recession affected the physical activity of young adults in the United States.

The study by Dickinson College economist Shamma Alam and Harvard T. H. Chan School of Public Health economist Bijetri Bose looked at Panel Study of Income Dynamics (PSID) data for young adults age 18 to 27--a phase of development associated with maturation and significant social, psychological and economic changes. They found that job losses experienced by the individual during the Great Recession reduce the likelihood of physical exercise by a significant 6.3 percentage points. This as action plans established by the World Health Organization and United Nations call for a 10 percent reduction in physical inactivity by 2025 and 2030, respectively.

"Our study finds that young adults from the Great Recession, who form the core part of the millennial generation today, suffered from significantly lower physical activity, which typically leads to worse physical health outcomes such as increased obesity," said Alam. "The Great Recession--considered the longest since the Great Depression--presents enormous economic implications and lessons that are relevant for the current COVID-19 induced economic downturn."

While the Great Recession had a disproportionately high 19% unemployment rate among young adults, unemployment for young adults during the COVID-19 pandemic has been much higher, peaking in 2020 at approximately 33 percent for those age 16-19; 26 percent for those age 20-24; and 16 percent for those age 25-29. Additionally, according to Pew Research, young adults age 18-29 also have--more than any other age group-- used money from their savings or retirement account, borrowed money from friends or family and received unemployment benefits since the coronavirus hit in February 2020.

Alam suggested these known decreases in physical activity during significant economic downturns also could have implications for the mental health of young adults. "Physical activity significantly went down following job losses during a major recession like the Great Recession likely because of negative mental health outcomes suffered by the individuals. When individuals are worried about their jobs and livelihood, they do not feel like exercising. Therefore, we are likely to see similar effects on physical activity during the current COVID-19 induced recession," said Alam, adding that in addition to job losses, stay-at-home orders had negative effect on young adults' mental health, which may then negatively affect physical activity.

Credit: 
Dickinson College

Better endurance and reliable data retention: A new STT-MRAM Quad technology

image: Figure 1: A schematic illustration of the new advanced Quad-MTJ technology concept. Based on Quad-interface technology with high retention over 10-years, advanced Quad-MTJ realizes a high endurance property by introducing (i) low RA MgO barrier, (ii) low magnetic dumping in recording layer, and (iii) stable reference layer.

Image: 
IEEE & Tohoku University

Professor Tetsuo Endoh's Group at Tohoku University's Center for Innovative Integrated Electronics has announced a new magnetic tunnel junction (MTJ) quad-technology that provides better endurance and reliable data retention - over 10 years - beyond the 1X nm generation.

This novel Quad technology meets the design requirements for the state-of-the-art X nm complementary metal-oxide semiconductor (CMOS) node and will pave the way for ultra-low-power consumption for Internet of Things (IoT) edge-devices in mobile communication, the automotive industry, consumer electronics, and industrial/infrastructure equipment.

The results will be presented in June at an international conference on semiconductor ultra-large scale integrated circuits entitled "2021 Symposia on VLSI Technology and Circuits." The conference takes place from June 13 to 19.

Developing smart societies through the use of the IoT, AI, and networks based on the next-generation mobile communication systems requires edge devices to be more power-efficient. A greater power efficiency also aids the goal of becoming carbon neutral.

Many logic circuits embedded with spin transfer-torque magnetoresistive random access memory (STT-MRAM) as a low power consumption technology. However, meeting the design rules of the X nm CMOS requires the MTJ diameter to be formed using the back end of line (BEOL) process and must fabricate at 1X nm generation.

The developed Quad-interface MTJ (Quad MTJ) - the first of its kind - has three new technologies: (i) a low RA technology, (ii) a low damping material in the recording layer, and (iii) a stable reference layer.

This enabled it to have (1) better retention characteristics of over 10 years, (2) endurance that exceeded at least 6 X 1011, (3) a high-speed write operation of 10 nanoseconds, (4) a low power consumption operation of 20%, and (5) a low write error rate combined with a circular diameter of 18 nm. Additionally, the Quad-MTJ has high retention and high endurance characteristics at a 10 ns high-speed operation. This is the first time in the world that severe conditions 1 - 5 have been realized at the 1X nm generation.

The 18nm Quad-MTJ possesses a large capacity STT-MRAM technology that is smaller than static random access memory (SRAM). As such, it is expected to replace SRAM for the X nm generation in CMOS logic. This means that STT-MRAM's application can expand to the leading-edge logic, achieving ultra-power consumption, excellent scalability and high reliability in application processors.

Credit: 
Tohoku University

How platelets help resolve lung inflammation

image: Platelets (red) interacting with regulatory T cells (yellow) in the bacterially inflamed lung tissue of a mouse. Researchers examined the living tissue using confocal fluorescence microscopy.

Image: 
Rossaint et al./JExpMed 2021

Treating patients with acute respiratory failure is a constant challenge in intensive care medicine. In most cases, the underlying cause is lung inflammation triggered by a bacterial infection or - more rarely, despite being frequently observed at present due to the corona pandemic - a viral infection. During the inflammation, cells of the immune system - the white blood cells - migrate to the lungs and fight the pathogens. At the same time, however, they also cause "collateral damage" in the lung tissue. If the inflammatory reaction is not resolved in time, this can result in chronic inflammation with permanent impairment of lung function. Together with colleagues from London, Madrid and Munich, a research team at the University of Münster headed by Prof Jan Rossaint and Prof Alexander Zarbock, two specialists in anaesthesiology and intensive care medicine, has gained new insight into the cellular processes involved in bacterial lung inflammation. In a study on mice, the researchers found that the interaction between platelets and certain white blood cells - the regulatory T cells - play a significant role in resolving the inflammation. The study has been published in the Journal of Experimental Medicine.

Platelets partner with regulatory T cells and send signals to scavenger cells

It was already known that, at the beginning of an inflammatory reaction in the lungs, as is the case with other organs, platelets work together with neutrophil granulocytes - a subgroup of white blood cells that specialize in fighting off pathogens. However, for the first time, the team of scientists has now shown that, as the inflammation progresses, platelets bind to regulatory T cells and that this binding is needed for the migration of the T cells, together with the platelets, to the site of inflammation in the lungs. Upon their arrival, they work together secreting anti-inflammatory messenger substances which "reprogramme" the macrophages in the lungs. These white blood cells, also known as scavenger cells, then stop directing neutrophil granulocytes to the site of inflammation, instead eliminating the neutrophil granulocytes that are no longer needed. This helps the inflammation subside and prevents further tissue damage.

Search for new therapy concepts

"When treating patients with acute lung failure, we have various measures we can take to support lung function and focus on combating the causative pathogens with antibiotics, for example," explains Jan Rossaint. "However, we lack other therapeutic options which can be used to target the causes and regulate the course of the inflammation." These latest investigations have provided a basis for such therapy concepts. In further steps, the researchers will examine whether the inflammatory mechanisms they observed in mice also occur in humans and look for starting points to test specific therapies.

Credit: 
University of Münster

Activation of carbon-fluorine bonds via cooperation of a photocatalyst and tin

image: The world's first regioselective C-F bond transformation of perfluorinated compounds.

Image: 
Osaka University

Fluorinated compounds are an important group of compounds that are widely used in pharmaceuticals, agricultural chemicals, functional resins, and organic electronic materials. In particular, perfluorinated compounds with multiple carbon-fluorine bonds are attracting attention because of their high thermal and chemical stability and various excellent properties such as water and oil repellency and chemical resistance.

"C-F bonds are extremely strong; hence, their transformation under mild conditions is difficult, and the selective activation of a specific C-F bond from among multiple C-F bonds in perfluorinated compounds has not been achieved," explains Prof. Makoto Yasuda, corresponding author of the study.

The research team led by Prof. Makoto Yasuda has discovered that a site-selective C-F bond transformation to valuable functional groups proceeds via a photocatalyst and organotin compounds under visible light irradiation (Figure. 1). Experimental and theoretical results revealed the importance of the cooperation of a photocatalyst and organotin compounds in this transformation.

In this research, site-selective C-F bond transformation to valuable allylic groups has been accomplished by using a photocatalyst and organotin compounds under safe and common visible light irradiation (Figure 2a). The establishment of the methodology to activate strong carbon-fluorine bonds under such mild conditions is the key to achieving the targeted transformation of perfluorinated compounds at specific sites.

"We have attempted to elucidate this reaction mechanism using both experimental and theoretical chemical methods and have found that the cooperative action of the photocatalyst and organotin compound plays a very important role in the progression of the reaction. In particular, it is noteworthy that the organotin compound plays the dual role of capturing unstable radical intermediates and scavenging fluorine as a Lewis acid, which is a very significant finding for future research on carbon-fluorine bond conversion reactions," explains Prof. Makoto Yasuda. Furthermore, by using this method, they have succeeded in synthesizing fluorine-substituted analogues of a compound that show promise for pharmaceutical applications (Figure 2b).

"Fluorine is an important element in pharmaceuticals, and many small-molecule drugs contain fluorine atoms. It is expected that the field of fluorine-containing drugs will continue to grow. As a result of this research, high value-added perfluorinated compounds, which were impossible to synthesize in the past, can now be synthesized in a simple and short process, which is expected to lead to the expansion of the library of seed compounds for fluorine-containing drug discovery," says Prof. Makoto Yasuda.

Credit: 
Osaka University

A speedy trial: What it takes to be the fastest land predator

image: (Left) Flight types involved in cheetah galloping (Right) A simple model for analyzing galloping motion. A team of researchers from Japan devised a simple analytical model emulating vertical hopping and spine bending movement displayed by cheetahs during running and obtained criteria for determining flight types like cheetah galloping

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Image courtesy: Tomoya Kamimura from Nagoya Institute of Technology

What makes cheetah the fastest land mammal? Why aren't other animals, such as horses, as fast? While we haven't yet figured out why, we have some idea about how--cheetahs, as it turns out, make use of a "galloping" gait at their fastest speeds, involving two different types of "flight": one with the forelimbs and hind limbs beneath their body following a forelimb liftoff, called "gathered flight," while another with the forelimbs and hind limbs stretched out after a hind limb liftoff, called "extended flight" (see Figure 1). Of these, the extended flight is what enables cheetahs to accelerate to high speeds, and it depends on ground reaction forces satisfying specific conditions; in the case of horses, the extended flight is absent.

Additionally, cheetahs show appreciable spine movement during flight, alternating between flexing and stretching in gathered and extended modes, respectively, which contributes to its high-speed locomotion. However, little is understood about the dynamics governing these abilities.

"All animal running constitutes a flight phase and a stance phase, with different dynamics governing each phase," explains Dr. Tomoya Kamimura from Nagoya Institute of Technology, Japan, who specializes in intelligent mechanics and locomotion. During the flight phase, all feet are in the air and the center of mass (COM) of the whole body exhibits ballistic motion. Conversely, during the stance phase, the body receives ground reaction forces through the feet. "Due to such complex and hybrid dynamics, observations can only get us so far in unraveling the mechanisms underlying the running dynamics of animals," Dr. Kamimura says.

Consequently, researchers have turned to computer modeling to gain a better dynamic perspective of the animal gait and spine movement during running and have had remarkable success using fairly simple models. However, few studies so far have explored the types of flight and spine motion during galloping (as seen in a cheetah). Against this backdrop, Dr. Kamimura and his colleagues from Japan have now addressed this issue in a recent study published in Scientific Reports, using a simple model emulating vertical and spine movement.

The team, in their study, employed a two-dimensional model comprising two rigid bodies and two massless bars (representing the cheetah's legs), with the bodies connected by a joint to replicate the bending motion of the spine and a torsional spring. Additionally, they assumed an anterior-posterior symmetry, assigning identical dynamical roles to the fore and hind legs.

By solving the simplified equations of motion governing this model, the team obtained six possible periodic solutions, with two of them resembling two different flight types (like cheetah galloping) and four, only one flight type (unlike cheetah galloping), based on the criteria related to the ground reaction forces provided by the solutions themselves. Researchers then verified these criteria with measured cheetah data, revealing that cheetah galloping in the real world indeed satisfied the criterion for two flight types through spine bending (see Figure 2).

Additionally, the periodic solutions also revealed that horse galloping only involves gathered flight due to restricted spine motion, suggesting that the additional extended flight in cheetahs combined with spine bending allowed them to achieve such great speeds!

"While the mechanism underlying this difference in flight types between animal species still remains unclear, our findings extend the understanding of the dynamic mechanisms underlying high-speed locomotion in cheetahs. Furthermore, they can be applied to the mechanical and control design of legged robots in the future," speculates an optimistic Dr. Kamimura.

Cheetahs inspiring legged robots! Who would've thought?

Credit: 
Nagoya Institute of Technology

Luring bacteria into a trap

Developing vaccines against bacteria is in many cases much more difficult than vaccines against viruses. Like virtually all pathogens, bacteria are able to sidestep a vaccine's effectiveness by modifying their genes. For many pathogens, such genetic adaptations under selective pressure from vaccination will cause their virulence or fitness to decrease. This lets the pathogens escape the effects of vaccination, but at the price of becoming less transmissible or causing less damage. Some pathogens, however, including many bacteria, are extremely good at changing in ways that allow them to escape the effects of vaccination while remaining highly infectious.

For scientists looking to develop vaccines, this kind of immune evasion has been a fundamental problem for decades. If they set out to develop vaccines against bacterial pathogens, often they will notice that these quickly become ineffective.

Weaponising immune evasion

Now, however, researchers at ETH Zurich and the University of Basel have exploited precisely this mechanism to come up with an effective vaccine against bacteria. They succeeded in developing a Salmonella vaccine that, instead of trying to outright kill intestinal bacteria, rather guides their evolution in the gut to make them a weaker pathogen.

"This allowed us to show that immune evasion is not only a major challenge in vaccine development, but that it can in fact be put to good use in both human and veterinary medicine," explains ETH Professor Emma Slack. "We can use it to drive the evolution of pathogenic microorganisms in a certain direction - in our case, a dead end." Slack led the study, which involved many researchers from different groups at ETH Zurich and other institutions, together with ETH Professor Wolf-Dietrich Hardt and Médéric Diard, Professor at the University of Basel's Biozentrum.

Combination vaccine leads to the goal

In their study, the researchers inoculated mice with a series of slightly different vaccines against Salmonella typhimurium, and observed how the Salmonella in the animals' guts modified their genes to escape the vaccines' effects. This let the scientists identify the full spectrum of possible immune evasion mutations in Salmonella typhimurium. Subsequently, the researchers produced a combination vaccine from four Salmonella strains that covered the bacteria's full spectrum of genetic evasion options.

A surprising immune evasion was driven by this combined vaccine, causing an important Salmonella sugar coating on the surface to atrophy. While the affected bacteria were still able to multiply in the animals' guts, they were largely unable to infect body tissues and cause disease. This is because the sugar coating is part of the bacteria's protective coating that shields them from the host's defences as well as from viruses that often infect and kill the bacteria. In tests on mice, the scientists were able to show that their new vaccine was more effective at preventing Salmonella infections than existing vaccines approved for use in pigs and chickens.

The scientists now plan to use the same principle to develop vaccines against other microorganisms - for example, against antimicrobial-resistant bacterial strains. In addition, it ought to be possible to use the approach in biotechnology and bring about specific modifications in microorganisms by exerting selective pressure through vaccines.

Credit: 
ETH Zurich

Researchers figured out how the ancestors of modern horses migrated

image: Caballine horse descendants now live in Canada, USA, China, Russia and Kazakhstan.

Image: 
UrFU

An international research team determined that ancestors of modern domestic horses and the Przewalski horse moved from the territory of Eurasia (Russian Urals, Siberia, Chukotka, and eastern China) to North America (Yukon, Alaska, continental USA) from one continent on another at least twice. It happened during the Late Pleistocene (2.5 million years ago - 11.7 thousand years ago). The analysis results are published in the journal. The findings and description of horse genomes are published in the journal Molecular Ecology.

"We found out that the Beringian Land Bridge, or the area known as Beringia, influenced genetic diversity within horses and beyond," said senior researcher at the Ural Branch of the Russian Academy of Sciences and the Ural Federal University (Russia) Dmitry Gimranov. "Owing to the appearance of this land part, the flow of genes among mammoths, bison, and wolves could occur regularly. And if 1-0.8 million years ago horses from North America were not yet widespread in Eurasia, then in the periods of 950-450 and 200-50 thousand years ago, there was a bidirectional spread of genes over long distances."

In other words, horses migrated between continents not only in one direction but also vice versa. The first wave of migration was predominantly from North America to Eurasia. The second migration was dominated by the movement from Eurasia to North America.

The most important researchers conclude that most animals used the Beringian Land Bridge only once, and horses several times. This fact could significantly affect the genetic structure of horse populations and made them very interesting objects of research for paleogeneticists.

To determine the area of settlement of horses, molecular biologists studied horses' DNA from both continents. From 262 samples of bones and teeth, they selected 78 with sufficient DNA. Researchers conducted radiocarbon dating and genetic analysis at the Denmark and USA laboratories. In addition, they looked at the research data from 112 samples.

"The data shows that horses returned to North America from Eurasia across Beringia at about the same time as bison, brown bears, and lions," says Dmitry Gimranov. "That is, in the last "days" of the late Pleistocene, when the territory was not covered by water and it was like a bridge for the movement of many groups of animals. With the beginning of climate warming (the beginning of the Holocene or 11.7 thousand years ago) and the last disappearance of Beringia at the end of the Pleistocene, the biogeographic significance of this ecological corridor radically changed the history of terrestrial animal species on both continents."

Although the North American horse population eventually became extinct in the early Holocene, horses became widespread on both continents due to domestication and are now found far beyond their historical range.

Credit: 
Ural Federal University

Aortic condition more deadly in women than in men

CHICAGO -- Women who experience acute aortic dissection--a spontaneous and catastrophic tear in one of the body's main arteries--not only are older and have more advanced disease than men when they seek medical care, but they also are more likely to die, according to research published online today in The Annals of Thoracic Surgery.

"Data over the course of the last few decades demonstrate differences in both presentation and outcomes between males and females who have acute aortic dissection, with greater mortality among females," said Thomas G. Gleason, MD, from Brigham and Women's Hospital in Boston, Massachusetts. "This study underscores the need for further interrogatories into these sex differences that may help provoke refined sex-directed strategies to further improve outcomes."

Lauren Huckaby, MD, from the University of Pittsburgh in Pennsylvania, Dr. Gleason, and colleagues queried the Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) to explore sex-specific differences in presentation, operative approach, and outcomes in patients with type A acute aortic dissection (TAAD). IRAD is the largest consortium of centers worldwide (55 institutions in 12 countries) that collects and analyzes data related to the clinical aspects of aortic dissection; the IVC was initiated to provide more detailed insight into surgical techniques and procedures for aortic dissection.

The Stanford classification divides aortic dissections into two groups (A and B), depending on the location of the tear in the aorta. In type A dissection, the tear begins where the aorta exits the heart (ascending aorta) and frequently extends from the upper to lower sections of the aorta, compromising blood flow throughout the body. Type A aortic dissections have a high likelihood of migrating toward the heart, where they become deadly by rupturing into the pericardial sac that surrounds the heart. As many as 40% of people with aortic dissections die instantly, and the risk of death increases approximately 1% for every hour that the diagnosis and surgical repair are delayed, according to multisociety clinical practice guidelines.

Within the IRAD-IVC database, the researchers identified 2,823 patients who experienced TAAD from 1996 to 2018 and underwent operative repair or a surgical approach as part of a hybrid repair. Approximately 34% of the patients were female.

Sex-Specific Differences in Clinical Presentation

Although less frequently affected by TAAD, female patients were significantly older than male patients (65.4 years versus 58.6 years on average) and had different presenting symptoms, like hypotension (low blood pressure) and greater evidence of malperfusion (loss of blood supply to a vital organ), with a higher prevalence of shock (31.3% versus 22.2%) and coma/altered consciousness (11.5% versus 7.5%).

Benjamin A. Youdelman, MD, from Maimonides Medical Center in Brooklyn, New York, who was not directly involved in this research, explained that these variances in clinical presentation indicate that women may be waiting longer to seek medical care compared to men. This may be due to female patients being "stoic," not considering their symptoms as signs of a significant problem and not prioritizing their care.

"The result is presenting for medical care later, with a greater percentage of women in shock and mental status changes that are often attributed to a stroke, which can further delay the correct diagnosis of an aortic dissection as the cause," said Dr. Youdelman, who works closely with the aortic disease awareness campaign--Think Aorta US. "All of this results in worse early outcomes after aortic dissection for women compared to men. It has been known for a long time that outcomes after aortic dissection are dependent on time to treatment: The faster a person is treated the better."

Variations in Imaging Findings

The researchers also found differences in imaging: Female patients were more likely to experience intramural hematoma, which is blood leaking through the innermost layer of the aortic wall and flowing between the inner and outer walls (19.4% versus 13.2%), and complete (17.2% versus 10.2%) or partial (24.8% versus 19.4%) false lumen thrombosis. In aortic dissection, the force of the diverted blood splits the aortic wall layers, leading to the formation of a false lumen or newly created passageway for blood flow.

"The recognition that women present differently and later in the course suggests that they may be seeking emergency care in a more delayed fashion than men," said Dr. Gleason. "Accordingly, clinicians should respond to these sometimes opaque signs and symptoms by considering aortic dissection early. These findings at presentation should raise suspicion among physicians into the possibility of aortic dissection, giving rise to immediate diagnosis to allow for more efficient surgical management. We should be hypervigilant in women to avoid any further delays in treatment."

Operative Approaches

The researchers noted that operative approaches were distinct between the sexes, with female patients being less likely than male patients to undergo aortic valve replacement, aortic root replacement, and/or complete arch replacement. In fact, the less frequent use of complete arch replacement in female patients (15.2% versus 20.6%) was highlighted by the researchers because worse outcomes after the operation historically have been demonstrated. They deduced that this more aggressive approach may be avoided in the treatment of older, female patients due to concerns for worse outcomes.

Overall, female patients had increased mortality, although in the last few years, mortality between the sexes was comparable, which suggests recent improvements in care. According to Dr. Gleason, better recognition, earlier diagnosis, faster and more efficient care delivery, new and improved surgical techniques--including brain perfusion and reconstruction procedures--and subsequent longitudinal surveillance have all contributed to more lives being saved.

Dr. Youdelman explained that family medical history also is a critically important factor for identifying patients at risk and saving lives. "Once this information is shared with the health care team, an evaluation by CT scan to achieve definitive diagnosis and rapid treatment would result. Patients should start conversations with their families; it may save a life," he said.

Further study by the researchers is expected in order to better understand what is driving the development of acute aortic syndromes in each sex, as well as more accurately determine dissection risk and inform individualized treatment decisions.

Credit: 
The Society of Thoracic Surgeons

Researchers explore ways to detect 'deep fakes' in geography

image: Researchers combined satellite images of Tacoma, Washington, with Seattle and Beijing to create a composite image, and then identified differences between the false and true images.

Image: 
Chengbin Deng

Can you trust the map on your smartphone, or the satellite image on your computer screen?

So far, yes, but it may only be a matter of time until the growing problem of "deep fakes" converges with geographical information science (GIS). Researchers such as Associate Professor of Geography Chengbin Deng are doing what they can to get ahead of the problem.

Deng and four colleagues -- Bo Zhao and Yifan Sun at the University of Washington, and Shaozeng Zhang and Chunxue Xu at Oregon State University -- co-authored a recent article in Cartography and Geographic Information Science that explores the problem. In "Deep fake geography? When geospatial data encounter Artificial Intelligence," they explore how false satellite images could potentially be constructed and detected. News of the research has been picked up by countries around the world, including China, Japan, Germany and France.

"Honestly, we probably are the first to recognize this potential issue," Deng said.

Geographic information science (GIS) underlays a whole host of applications, from national defense to autonomous cars, a technology that's currently under development. Artificial intelligence has made a positive impact on the discipline through the development of Geospatial Artificial Intelligence (GeoAI), which uses machine learning -- or artificial intelligence (AI) -- to extract and analyze geospatial data. But these same methods could potentially be used to fabricate GPS signals, fake locational information on social media posts, fabricate photographs of geographic environments and more.

In short, the same technology that can change the face of an individual in a photo or video can also be used to make fake images of all types, including maps and satellite images.

"We need to keep all of this in accordance with ethics. But at the same time, we researchers also need to pay attention and find a way to differentiate or identify those fake images," Deng said. "With a lot of data sets, these images can look real to the human eye."

To figure out how to detect an artificially constructed image, first you need to construct one. To do so, they used a technique common in the creation of deep fakes: Cycle-Consistent Adversarial Networks (CycleGAN), an unsupervised deep learning algorithm that can simulate synthetic media.

Generative Adversarial Networks (GAN) are a type of artificial intelligence, but they require training samples -- input -- of whatever content they are programmed to produce. A black box on a map could, for example, represent any number of different factories or businesses; the various points of information inputted into the network helps determine the possibilities it can generate.

The researchers altered a satellite image of Tacoma, Washington, interspersing elements of Seattle and Beijing and making it look as real as possible. Researchers are not encouraging anyone to try such a thing themselves -- quite the opposite, in fact.

"It's not about the technique; it's about how human being are using the technology," Deng said. "We want to use technology for the good, not for bad purposes."

After creating the altered composite, they compared 26 different image metrics to determine whether there were statistical differences between the true and false images. Statistical differences were registered on 20 of the 26 indicators, or 80%.

Some of the differences, for example, included the color of roofs; while roof colors in each of the real images were uniform, they were mottled in the composite. The fake satellite image was also dimmer and less colorful, but had sharper edges. Those differences, however, depended on the inputs they used to create the fake, Deng cautioned.

This research is just the beginning. In the future, geographers may track different types of neural networks to see how they generate false images and figure out ways to detect them. Ultimately, researchers will need to discover systematic ways to root out deep fakes and verify trustworthy information before they end up in the public view.

"We all want the truth," Deng said.

Credit: 
Binghamton University

Rush researchers develop new measure of brain health

How old is your brain compared to your chronological age? A new measure of brain health developed by researchers at Rush University Medical Center may offer a novel approach to identifying individuals at risk of memory and thinking problems, according to research results published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association on June 1.

Dubbed the "cognitive clock" by the researchers, the tool is a measure of brain health based on cognitive performance. It may be used in the future to predict the likelihood of memory and thinking problems that develop as a person ages.

"Alzheimer's disease, which is of the most common cause of dementia, and other diseases of the brain accumulate slowly over time as people get older. Age is widely recognized as the main risk factor for Alzheimer's disease, but it's a very imperfect predictor, since not everyone develops dementia as they age," said Patricia Boyle, PhD, professor in Rush Medical College's Division of Behavioral Sciences neuropsychologist in the Rush Alzheimer's Disease Center (RADC), and lead author of the study.

"Our new cognitive clock provides a measure of brain health that tells us more about how well a person's brain is functioning than chorological age. In this way, the clock can help us detect who is at highest risk of developing cognitive impairment in the coming years.

"For some people, cognition remains fairly stable as they age," Boyle added. "But, for others, cognition declines slowly over time, and still others show steep declines."

The researchers believed that cognitive performance data, even using a simple cognitive screening test, could be used to distinguish people exhibiting normal cognitive aging from those who are on their way to developing memory and thinking problems that are often coupled with aging.

This thesis led the Rush researchers to look at data they acquired from several long-term studies conducted by the RADC, including the Rush Memory and Aging Project (MAP) which included people living in the community in greater Chicago; the Religious Orders Study (ROS), which included older Catholic clergy from across the United States; and the Chicago Health and Aging Project (CHAP), a biracial population-based study.

"We used long-term cognitive testing data from our participants to develop a profile of cognitive aging, what we call the cognitive clock" Boyle said. "The cognitive clock reflects the general pattern of age-related cognitive decline and allows us to see who is doing better than average and who is doing worse at a given point in time. This helps us identify who might be at high risk of developing memory and thinking problems."

The cognitive clock was first developed working with data from 1057 participants from the MAP and the ROS, who began without cognitive impairment and underwent yearly cognitive assessments for up to 24 years. The cognitive assessment included the Mini-Mental State Exam, a widely used test of cognitive function among the elderly that measures orientation, attention, memory, language and visual-spatial skills. In addition to the MMSE, detailed evaluations also included a structured medical history, neurologic examinations, and a set of neurocognitive tests.

The researchers examined how cognitive performance changes over time with advancing age using a novel statistical approach to identify the typical profile of cognitive aging. Using this cognitive clock, researchers can estimate an individual's cognitive age -- their position on the clock -- at any given point in time.

Cognitive age is an indicator of brain health. "We found that, on average, cognition remains stable until a cognitive age of around 80 years of age, then declines moderately until 90, then declines more rapidly until death," Boyle said.

"Further, we found that cognitive age is a much better predictor than chronological age of dementia, mild cognitive impairment and mortality. It also is more strongly associated with other aspects of brain health."

The researchers then applied the clock to an independent sample of 2,592 participants from CHAP to confirm its accuracy for predicting outcomes such as Alzheimer's dementia, mild cognitive impairment, and mortality. Again, they found that cognitive age was a better predictor of these outcomes than chronological age.

"Essentially, what we did is use cognitive data collected over many years to create a single, easy-to-understand metric that may be used to predict health outcomes with good accuracy," Boyle said.

This tool may serve as an aid in aging research moving forward and may offer a new tool to identify at risk individuals.

"It is very difficult to develop a test or biomarker that accurately predicts health outcomes on an individual level. This has been a longstanding challenge in aging research. However, we are hoping that with additional research and validation, we may be able extend the approach applied here to clinical settings," Boyle said.

"Ideally, we could have a patient come into a clinic or hospital and complete a brief cognitive screen that gives us information to plug into a formula to estimate their cognitive age. That will provide important information about their brain health, and from there, we can estimate likelihood of developing Alzheimer's disease or dementia in the coming years. That would be an exciting advance."

Credit: 
Rush University Medical Center