Culture

A tiny flatworm found commonly on the coasts of western Europe and North America is living proof that species may be able to evolve and adapt to rapid climate change.

Research by the University of Plymouth examined the extent to which the intertidal flatworm Procerodes littoralis was able to regenerate and repair itself when challenged with different sea water conditions.

Repeating a study conducted more than a century earlier it was shown that the response of individuals had changed markedly since then.

The original study was conducted by Dorothy Jordan Lloyd, who was based at the Marine Biological Association in Plymouth, and focussed on individuals found in Wembury Bay, Plymouth.

It was published in 1914, and the current study - led by BSc (Hons) Marine Biology graduate Katharine Clayton - replicated it in terms of the processes followed and the precise locations from which samples were collected.

When tested across a range of different concentrations of salt water in the laboratory, scientists showed the flatworm was able to regenerate following minor injuries at lower salinities than were recorded originally.

They also demonstrated that while in 1914 there was an optimum salinity level for individuals to regenerate this is no longer the case, suggesting individuals have extended their tolerance range in the intervening 104 years.

Scientists also examined rainfall levels for the Wembury Bay area and found they had increased between 1914 and 2018, which is likely to result in exposure to lower salinities in the intertidal region, where the flatworm is found.

Put together, they say it shows how individual species may be able to adapt and survive the localised effects of climate change which, if correct, provides some of the first evidence of evolutionary rescue taking place in the wild.

Katharine Clayton began the study as part of her undergraduate degree and wrote it up for her final year dissertation. Now pursuing a PhD at the University of Exeter, she said: "When we first began looking at this flatworm, we were interested in how it tolerated salinity levels in it natural habitat. However, we quickly found out about Dorothy's study in 1914 so it became a perfect test of how an individual population had adapted to changes within its immediate environment. The findings provide really interesting evidence of the impacts of climate change, but it has also been inspiring for me to revisit Dorothy's work and highlight a pioneering female scientist of her time."

The research's co-author, Professor of Marine Zoology John Spicer, supervised Katharine's work and is a world-leading authority on how marine species can adapt to climate change. He added: "There has been an idea around for the last 15 to 20 years called evolutionary rescue where, faced with rapid climate change, animals evolve to survive. Many, including myself, have doubted the possibility of such rescue, especially over such a short space of time in terms of species evolution. But this study shows it may well be possible in the wild because, in comparing two identical experiments 100 years apart, the animal has changed how it works, its physiology.

"It is proof that evolutionary rescue may exist in the wild, not just in the laboratory, and is a major step forward in our understanding of how species can adapt as the environment around them changes. With the two studies being conducted 50 years before and after the start of the Anthropocene, it also provides a fascinating insight into the effect humans are having on species with whom we share our planet."

This news is embargoed until Oct. 1, 2020, 11:00 a.m. ET and should follow the announcement of the EHT collaboration, which will also be posted via EurekAlert!.

If a picture is worth a thousand words, what might the first horizon-scale image of a black hole tell us? A new paper by researchers from the Event Horizon Telescope (EHT) collaboration, which famously imaged M87's central black hole, has provided a number of enlightening answers. Based on an analysis of the black hole's shadow, the team conducted a unique test of general relativity, deepening understanding about the unusual properties of black holes and ruling out many alternatives. This research, published in Physical Review Letters, was led by Dimitrios Psaltis (IAS Member, 2001-03) of the University of Arizona, Lia Medeiros of the Institute for Advanced Study (IAS), and Feryal Özel (IAS Member, 2002-05) and Pierre Christian, both of the University of Arizona, and was co-authored by the EHT collaboration.

The intense gravity of a black hole curves spacetime, acting as a magnifying glass and causing the black hole shadow to appear larger. By measuring this visual distortion, the research team found that the size of the black hole shadow corroborates the predictions of general relativity. A test of gravity at the edge of a supermassive black hole represents a first for physics and offers further proof that Einstein's theory remains intact even under the most extreme conditions.

"This is really just the beginning. We have now shown that it is possible to use an image of a black hole to test the theory of gravity," explained Medeiros. "This test will be even more powerful once we image the black hole in the center of our own galaxy and in future EHT observations with additional telescopes that are being added to the array."

The black hole shadow is unlike the shadows encountered in everyday life. Whereas a physical object casts a shadow by preventing light from passing through it, a black hole can create the effect of a shadow by siphoning light towards itself. While light cannot escape from the interior of a black hole, it is possible--though unlikely--for light to escape from the region surrounding the event horizon, depending on its trajectory. The result is a murky no man's land just beyond the point of no return, which appears to observers as a shadow.

Gravitational tests have been conducted in a variety of cosmic settings. During the 1919 solar eclipse, the first evidence of general relativity was seen based on the displacement of starlight, traveling along the curvature of spacetime caused by the sun's gravity. More recently, tests have been conducted to probe gravity outside the solar system and on a cosmological scale. Examples include the detection of gravitational waves at the Laser Interferometer Gravitational-Wave Observatory (LIGO). Gravitational waves propagate through the fabric of spacetime like ripples on a pond given the dynamic nature of spacetime as predicted by general relativity.

The new EHT paper focuses on a previously unexplored parameter space for black hole research. In addition to providing a brand-new test for all alternative formulations of gravity, it also connects the constraints from black hole images to those from other gravitational experiments. The supermassive black hole at the center of M87 studied by the EHT collaboration is 6.5 billion times more massive than the sun. In contrast, gravitational wave detectors monitor stellar mass black holes that range from five to several dozen solar masses. Such diverse perspectives are essential to a more comprehensive understanding of the underlying nature of black holes.

The nearly circular shape of the black hole shadow, as observed, may also lead to a test of the general relativistic no-hair theorem, which states that a black hole is described entirely by its mass, spin, and electrical charge. In other words, two black holes that possess the same mass, spin, and electrical charge would be considered indistinguishable--similar to the identical nature of like subatomic particles. Should geometric irregularities be detected it would potentially indicate the existence of additional black hole properties beyond mass, spin, and electrical charge.

In a separate study, "A Parametric Model for the Shapes of Black Hole Shadows in Non-Kerr Spacetimes," published in The Astrophysical Journal this year, Medeiros, Psaltis, and Özel explore the size and shape of the black hole shadow by modeling several different spacetimes and theories of gravity. The black hole shadow depends only on the geometry of the surrounding spacetime and not on the astrophysics of the accretion process.

The ongoing work of the EHT collaboration and its members will continue to bring light to both the hidden framework and visible features of black holes.

The human gut contains a diverse ecosystem of microbes: mainly bacteria, as well as viruses and fungi, termed the gut microbiota. Recent years have shown that the gut microbiota have widespread effects on the overall functioning of the host's body.

Normally infants receive gut bacteria from the mother at birth. Some of these maternal bacteria grow out in the infant as they aid the infant in digesting breast milk.

Birth by Cesarean section (C-section) has been shown to be especially detrimental to normal gut microbiota development. During birth by C-section infants are not exposed to maternal fecal microbes and this prevents the natural transfer of microbes from mother to baby.

In the recently reported study, researchers of mainly the University of Helsinki evaluated whether the disturbed intestinal microbiota development could be restored in term Cesarean section infants by postnatal, orally-delivered maternal fecal microbiota transplantation (FMT). FMT has been successfully used in adults to normalize gut microbiota composition and cure diseases such as recurrent Clostridium difficile infections.

The results of the study are published in the scientific journal Cell.

"Birth by C-section is associated with an increased risk of many immune-related diseases, suggesting that the lack of maternal microbes in early life may have long-term consequences on the health of the child. This proof-of-concept study demonstrates that the intestinal microbiota of infants born by C-section can be postnatally restored by maternal FMT and provides further support for the natural transfer of gut microbiota from mother to infant," says Willem M de Vos, Professor of Human Microbiomics who was a senior author on the study.

The procedure reduces risks that abnormal gut microbiota may confer

The researchers applied FMT immediately after birth by using the infants' own mothers' fecal samples. Because feces can contain dangerous pathogens, these were first carefully screened. Out of 17 tested mothers, 7 had pathogen-free samples and were selected for the study.

All seven C-section born infants that received the FMT remained healthy and experienced no negative effects from the treatment. Their gut microbiota composition was monitored for 3 months and compared the composition to that of untreated C-section born infants and vaginally born infants.

"The gut microbiota of the FMT-treated infants became very quickly similar to that of vaginally born infants. It did not resemble that of the untreated C-section born infants, showing that the treatment was effective in restoring normal microbiota development," says Dr. Katri Korpela, first author on the study.

"This simple procedure can normalize gut microbiota colonization and development in C-section born infants, which will likely contribute to reduced risk of developing chronic diseases that abnormal gut microbiota may confer," adds Dr. Otto Helve MD, specialist in pediatric infectious diseases and shared first author of the study.

"This procedure should be only performed after careful screening of the mother for potential pathogens," stresses Professor Sture Andersson MD, neonatologist who also was a senior author on the publication.

The evolution of epidemic and endemic strains of the cholera-causing bacterium Vibrio cholerae in Argentina has been mapped in detail by researchers at the Wellcome Sanger Institute, the London School of Hygiene and Tropical Medicine, the University of Cambridge and the INEI-ANLIS "Dr Carlos G. Malbrán", Argentina. The teams used whole genome sequencing to study the bacteria circulating during the 1991-1998 outbreak of cholera in the country.

The data have influenced health policy in Argentina, where the national alert surveillance system now uses whole-genome sequencing to distinguish between pandemic and non-pandemic lineages of V. cholerae bacteria. The study is published in Nature Communications today (1 October).

Cholera, caused by strains of V. cholerae bacteria, currently affects 47 countries world-wide and claims the lives of nearly 100,000 people a year*. Since the 1800s, there have been seven cholera pandemics around the globe, causing millions of deaths. The current pandemic, which began in the 1960s, is caused by a single lineage of V. cholerae, called 7PET. While South and Central Latin America have largely recovered from the outbreaks that began in Haiti in 2010, the lineage continues to circulate the globe and is the cause of the world's largest cholera epidemic, ongoing in Yemen, where hundreds of thousands have been infected**, ***.

In a new study, the team sequenced the genomes of a unique set of historical V. cholerae samples, held at INEI-ANLIS "Dr. Carlos G. Malbrán", the national reference laboratory of Argentina. By re-analysing the past, the international team of researchers hope to understand better the future patterns of disease, and to enable rapid alerts for new introductions of pandemic lineages.

Using phylogenetic analysis, they confirmed that the 1992 outbreak of cholera in Argentina was caused by one introduction of 7PET V. cholerae bacteria, originally introduced into Peru. The bacteria then evolved very little during the six years of the epidemic. This was in contrast to the diverse, multiple endemic strains of V. cholerae circulating at the same time. Previous work by the team has shown that while endemic strains can make people ill, they seem to lack the potential to spread quickly and cause an epidemic****.

Matthew Dorman, first author on the study from the Wellcome Sanger Institute said: "When a 7PET pandemic strain enters into Latin America from elsewhere, it can cause massive epidemics, such as those seen in Peru in the 1990s and Haiti in 2010. If we are to control cholera epidemics efficiently, it is vital that we are able to distinguish and understand the differences between the local, endemic V. cholerae that co-exist alongside 7PET during a cholera epidemic. Our study elaborated the genomic evolutionary history of these two types together in a single country, during a decade where there were major cholera outbreaks in this region."

The findings have been used by public health authorities in Argentina, where the national alert system has now been changed to distinguish between pandemic 7PET lineage and local V. cholerae lineages using whole-genome sequencing.

Dr Josefina Campos, senior author from INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina said: "Thanks to a comprehensive surveillance and reporting system, the reference laboratory in Argentina contains a snapshot of an entire epidemic. This gave us a unique opportunity to understand the detailed evolution of V. cholerae bacteria in our country. We will be able to use these data and this experience to inform how we monitor and respond to any future cholera outbreaks - bacteria that cause epidemics pose a very different risk to those that do not; this is simple information that is critical for disease control. We are the first national reporting system in the world to use genomic data to monitor cholera like this."

Professor Nick Thomson, senior author from the Wellcome Sanger Institute and the London School of Hygiene and Tropical Medicine said: "Detailed studies like this contribute to our growing understanding of how cholera is moving across the globe: evidence to inform improved control strategies as well as identify areas for further research. Our challenge is to better understand why such a simple bacterium continues to pose such a threat to human health, with this study we are a little step closer."

A study published in Science on October 2 suggests that prioritizing aquatic environments in conservation programs for the Amazon region can be up to six times more efficient than focusing on the protection of terrestrial species, as is usual.

The conclusion is based on simulations using georeferenced field data on species diversity, weather and topography, among other things. The simulations enabled the researchers to identify the most important areas for the conservation of each group of species.

When conservation planning focuses on terrestrial species, they found, the protection achieved for aquatic species is only 22% of that obtained for terrestrial species, whereas when it focuses on the animals that inhabit rivers and lakes, the benefits reach 84% of the protection for species that live on land for the same financial cost.

The study was supported by São Paulo Research Foundation - FAPESP and led by researchers at the University of São Paulo's Luiz de Queiroz College of Agriculture (ESALQ-USP) in Brazil and Lancaster University in the UK.

"We know more about terrestrial species and so they end up influencing the choice of priority areas for conservation. It's assumed that aquatic biodiversity will benefit to the same extent. We set out to see whether this was so, given the considerable differences between the two environments. We concluded that it wasn't and that prioritizing terrestrial biodiversity doesn't guarantee the same degree of protection for aquatic biodiversity," said Cecília Gontijo Leal, first author of the article. The study was conducted while she was on a postdoctoral research internship at ESALQ-USP with a scholarship from São Paulo Research Foundation - FAPESP.

Beyond land and water

In preparing the simulations, the group analyzed data for 1,500 terrestrial species (plants, birds, and beetles) and aquatic species (fish, dragonflies, other insects) collected in 377 localities and 99 forest river channels (igarapés) in Paragominas and Santarém, Pará state. In these two municipalities, more than 40% of the forest cover has been cleared to make way for agricultural activities.

The analysis started from the assumption that aquatic environments are not isolated but interconnected, as water permeates terrestrial ecosystems and transports nutrients and species, as well as playing an important role in many ecological processes.

"Rivers are normally used as borders for conservation units, and catchment areas aren't totally protected because they aren't well-represented. Xingu Indigenous Park in the state of Mato Grosso is a classic case. The headwaters are outside the area of the park, and all the effects of deforestation, however distant, reach the indigenous communities and the biodiversity inhabiting the protected territory," Leal said.

According to the researchers, the benefits can be six times greater when planning includes both aquatic and terrestrial biodiversity data, compared with the way it is done now. When no data is available, simply including connectivity as a factor at least doubles the efficiency of conservation. The group found that the change of approach to include connectivity alone would increase the benefits to aquatic species by 75%-100% in Paragominas and by 130%-175% in Santarém, practically without losses to terrestrial species and using the same amount of financial resources.

"Conservation planning is usually delimited by an area, or polygon, on which efforts will focus. This is typically based on knowledge of terrestrial biodiversity. In our study we analyzed a large amount of data and showed what should be obvious considering the importance of water in the region," said Silvio Ferraz, a professor at ESALQ-USP, Leal's postdoctoral research advisor and another co-author of the study.

"Especially in the Amazon, everything revolves around water. Nutrient, organic matter, and aquatic species all move on the surface. What we didn't expect was that if conservation focused on aquatic fauna and on maintaining this movement there would be such a large gain compared with the benefit when focusing solely on terrestrial biodiversity," Ferraz said.

Besides being more effective for biodiversity, the integrated approach has the advantage of costing the same amount. "What's most important is integrated planning. It doesn't cost more and doesn't mean significant losses for terrestrial biodiversity. On the contrary," Leal said. "Even in situations where the aquatic biodiversity data isn't as plentiful as ours, just including aquatic connectivity makes delimitation of the area to be conserved much more intelligent, doubling the protection for aquatic species."

Leal and Ferraz are members of the Sustainable Amazon Network (RAS), an initiative that has over 30 partner institutions in Brazil and elsewhere, with some 100 researchers and graduate students working together on science-based projects to strengthen sustainability in the region.

The group now plans to apply the approach to the entire Amazon region, compiling the available data. Extending the study area will reinforce the results and could serve as a guide to help prioritize areas for protection or even create new conservation units. The method could also be tested on other areas that are important to conservation outside the Amazon.

Freshwater ecosystems occupy less than 1% of Earth's surface and correspond to only 0.01% of all the water on the planet. Yet they are home to some 10% of all known species, including a third of all vertebrates.

Since 1970, the populations of freshwater environments have dwindled by 83%, while terrestrial environments have lost 40%. More than 80% of the world's freshwater fish species live in tropical regions including the Amazon.

A study in mice conducted by the UAB shows that social isolation worsens the effects of Alzheimer's disease, with hyperactivity levels reaching up to twice as much as in the pathology itself

- The research also confirms an increase in the asymmetric atrophy of the hippocampus, a brain area central to memory

- The study was published in a special edition of Frontiers in Psychiatry entitled Death and Mourning Processes in the Times of the Coronavirus Pandemic (COVID-19), dedicated to assessing the effects of this pandemic

Researchers at the Department of Psychiatry and Legal Medicine and at the Institut de Neurociències (INc) of the Universitat Autònoma de Barcelona (UAB) have conducted a study which allows estimating, from the viewpoint of translational neuroscience, the effects of isolation in the current pandemic scenarios in elderly patients with dementia. The findings also may serve as a guide to the rethinking of vital conditions after the Covid-19 crisis. The study was published in Frontiers in Psychiatry, in a special edition of Frontiers in Psychiatry entitled Death and Mourning Processes in the Times of the Coronavirus Pandemic (COVID-19), dedicated to assessing the effects of this pandemic.

The researchers analysed the effects of isolation in male mice models suffering from advanced stages of Alzheimer's disease through a series of behavioural tests, which could be compared to several areas found in elderly residence homes. They compared these results with mice models of Alzheimer's that were not isolated, and with other healthy animal models undergoing a normal ageing process. The study was conducted with male mice because these are more affected by Covid-19 and are also the ones to show more deterioration of the neuro-immuno-endocrine system and worse survival conditions when suffering dementia.

The main findings demonstrate that isolation exacerbates hyperactivity up to twice as normal in mice with Alzheimer's disease, and also causes the appearance of strange behaviours. This increase was demonstrated consistently in the gross motor skills, related to the movement of arms, legs, feet or the entire body. However, it also affected fine motor skills, small movements made by hands, wrists, fingers, toes, lips and tongue. The isolated animals showed emotional patterns comparable to anxiety and changes in their stress management strategies.

"The results are concerning, given that anxiety is one of the main neuropsychiatric symptoms associated with dementia, which produces a large burden on the caregiver and, in some cases, makes clinical management a challenge", points out Aida Muntsant, first autor of the research, which is included as part of her PhD thesis.

Effects of isolation on memory

Researchers also analysed the effects of isolation on other neuropathological variables, and obtained different results. "Although the characteristic variables of the disorder, like taupathy, were not modified, some others such as asymmetric hippocampal atrophy increased with isolation. This dysfunction was recently described in human patients with dementia and modelled here for the first time with animal models of Alzheimer's disease. The finding is important, given that asymmetry has been linked to greater vulnerability to stress factors", states Lydia Giménez-Llort, Professor in Psychiatry and researcher at the INc directing the study.

The study also confirmed that the mice suffering from Alzheimer's disease lost body and renal mass, effects which also have been observed in Covid-19 patients, although the loss was greater with those in isolation. The loss in spleen mass, an important organ of the peripheral immune system, was only observed in isolated animals.

Rethinking isolation among the elderly

"Thinking of what the post-Covid-19 era will be like for the elderly implies a great deal of effort in redesigning all conditions of life, interventions in care and rehabilitation, and the management of forced solitude as part of new physical distancing measures. Therefore, it is necessary and urgent to estimate the impact these measures will have on the more vulnerable elderly population, such as those suffering from dementia", the researchers point out.

The study also highlights the need for personalised interventions adapted to the heterogeneous and complex clinical profile of people with dementia, and to consider how all of this affects the obligations of caregivers, whether they be professionals or members of the patient's family.

COLUMBUS, Ohio -- We hear sounds in part because tiny filaments inside our inner ears help convert voices, music and noises into electrical signals that are sent to our brains for processing. Now, scientists have mapped and simulated those filaments at the atomic level, a discovery that shed lights on how the inner ear works and that could help researchers learn more about how and why people lose the ability to hear.

The findings, published last week in the Proceedings of the National Academy of Sciences, involve very fine filaments in the inner ear called tip links. When sound vibrations reach the inner ear, the vibrations cause those tip links to stretch and open ion channels of sensory cells within the inner-ear cochlea, a tiny snail-shaped organ that allows our brains to sense sound. When tip links open those channels, that act triggers the cochlear electrical signals that we interpret as sound.

Tip links are crucial to hearing; their malfunction causes hearing loss and balance disorders. Tip links are made of proteins -- cadherin-23 and protocadherin-15 -- that scientists have learned are involved in inherited deafness. Scientists knew that tip links were important to hearing and balance, but until this study, did not know how tip links were structured at the atomic level.

Essentially, said Marcos Sotomayor, associate professor of chemistry and biochemistry at The Ohio State University and lead author of the study, scientists previously had low-resolution images of tip links. This work gave them high-resolution images -- and showed a key connection between the two proteins that form tip links.

"Now, we can see down to the atom, and we can create physics-based movies of how these tip links respond to sound-generated forces," Sotomayor said. "That can tell us a great deal more about how these work and what happens when they stop working."

The researchers isolated parts of the tip-link proteins and used X-ray crystallography -- a method that allows scientists to obtain atomic-resolution structures of biomolecules -- to build atomic models of the complete tip-link part made of the protocadherin-15 protein, and of its connection to cadherin-23.

Work on these proteins started more than a decade ago when Sotomayor obtained the first structures of the tips of cadherin-23 and protocadherin-15 and discovered that these proteins interact using an extended molecular "handshake." In the study published last week, researchers showed that connection uses two molecular "handshakes" that strengthen the filament. These "handshakes" are thought to be essential for hearing and balance in inner ears of all vertebrates.

The researchers used atomic models to conduct computer simulations of tip links to see them in action.

"These are the most complete and advanced molecular models and simulations of the tip link to date and required the use of massive computational resources," Sotomayor said.

The simulations, performed on supercomputers from the Ohio Supercomputer Center, the Texas Advanced Computing Center and the Pittsburgh Supercomputing Center, used up to a thousand computing cores working in parallel for months. Those simulations revealed the complex dynamics of tip links when responding to sound. The simulation trajectories, similar to molecular "movies," highlight conditions in which tip links can behave as soft springs or stiff cables pulling on the ion channels that allow us to hear.

"The structures also reveal tip-link sites that are mutated in inherited deafness," Sotomayor said. "So we can try to understand what is happening with the tip links when you have these sites modified by mutations, not only by looking at the static structures but also at the simulated trajectories of tip links responding to sound."

All the parts of our ears are designed to transform sound waves into electrical signals for our brains to process. Sound first reaches the outer ear and then travels to the middle ear, where it hits the tympanic membrane that causes bones inside the middle ear to move. That movement causes the sound vibrations to continue into the inner ear, where, eventually, the vibrations reach the cochlea to become electrical signals for the brain. The process happens fast, in a few millionths of a second, but if any part of the system fails, the sound signal either becomes muddled or does not reach the brain at all.

Tip links are some of the smallest parts of an already tiny and complex system. They are attached to the tops of microscopic hairs that are much smaller than the hairs on your head or the fine hairs inside our ears that start to become visible in the mirror with age. The microscopic hairs in the inner-ear cochlea are located atop sensory cells called "hair cells" and are positioned in a bundle that moves with sound vibrations. The force of the hair-cell bundle movement causes the tip links to open very small channels that let positively charged ions move from outside the cell to inside the cell, creating the basis for the electrical signals that will move from the cochlea to the human brain.

Similar hair cells are located in the inner-ear vestibular system in charge of our sense of balance. When we move our heads, vestibular hair-cell bundles shear and stretch their tip links to trigger electrical signals that the brain uses to maintain our balance and gaze.

"If you don't have the tip link, you can't hear, and you can't balance," Sotomayor said. "They are essential."

This new understanding of the atomic structure of tip-link proteins, Sotomayor said, could help researchers and doctors understand more about why tip links fail -- and, potentially, how to prevent failure. The two proteins that form tip links, cadherin-23 and protocadherin-15, are also found in the brain and in eye photoreceptors. When these proteins are completely non-functional, profound deafness is accompanied by progressive blindness in a disease called Usher syndrome. The new structures of protocadherin-15 are guiding the efforts of various research groups trying to use engineered versions of this protein for Usher syndrome gene therapy.

A group of researchers at the University of Ottawa has been looking for ways to improve enzyme design methodologies and recently published their findings in Nature Communications.

Enzymes are used in many industrial and biotechnological applications. With their numerous beneficial properties, they are the most efficient catalysts known - they even have the power to accelerate chemical reactions by more than a billion times. But since the number of naturally occurring enzyme activities is limited, the number of applications also remains limited. While researchers have succeeded in creating artificial enzymes, their catalytic efficiency doesn't reach the same level as that of natural enzymes.

We talked to senior author Roberto Chica, Full Professor in the Department of Chemistry and Biomolecular Sciences at the University of Ottawa, to learn more about his findings.

Can you please tell us more about artificially designed enzymes?

"Over the past 20 years, researchers have successfully designed artificial enzymes from scratch for a variety of model organic transformations. This was done using a procedure called 'computational enzyme design' where a catalytic site was computationally built onto a pre-existing protein scaffold devoid of the target catalytic activity.

While successful, this approach has exclusively yielded artificial enzymes displaying catalytic efficiencies that are orders of magnitude lower than those of natural enzymes, requiring subsequent optimization using what is called 'directed evolution' to improve activity. Directed evolution is a process whereby random mutations are introduced into a protein to generate a large library of mutant enzymes, which are then screened to identify beneficial mutations. It often requires multiple rounds of random mutagenesis and screening to increase activity significantly."

How does your research relate to directed evolution?

"In our work, we reveal how directed evolution improves the catalytic efficiency of a computationally designed biocatalyst by approximately 1000-fold by tuning the ensemble of structural sub-states that the enzyme can sample to favor those that are catalytically competent.

Based on these observations, we engineer an artificial biocatalyst with a catalytic efficiency on par with that of the average natural enzyme."

What is the impactful discovery?

"We developed a novel computational procedure for enzyme design that is more accurate than previous methods because it allows to approximate the intrinsic flexibility of the protein scaffold used as a template for design."

Why is this important?

"This is important because previous methods focused on creating a stable structure that ignores the inherent dynamism in natural enzymes, which is crucial to their function (i.e. enzymes must "move" to be efficient catalysts).

Previously, it was not known whether an artificial enzyme displaying a catalytic efficiency on par with that of a natural enzyme could be computationally designed. We show that this is possible but only by using a structural ensemble of protein templates approximating conformational flexibility instead of a single template as previously done.

The results presented in our manuscript suggest that computational enzyme design using a structural ensemble could prevent the need for directed evolution by allowing catalytically competent sub-states to be sampled during the design procedure."

What are the potential applications of your research?

"If we could design, from scratch, enzymes that can catalyze any target chemical reaction with high efficiency, it would open the door to highly valuable biotechnologies that are currently inaccessible using natural enzymes."

Is there anything you'd like to add?

Yes, research took place from 2018 to 2020, at the University of Ottawa and the University of California, San Francisco.

When a star unleashes as much energy in a matter of days as our Sun does in several billion years, you know it's not going to remain visible for long.

Like intergalactic paparazzi, NASA's Hubble Space Telescope captured the quick, fading celebrity status of a supernova, the self-detonation of a star. The Hubble snapshots have been assembled into a telling movie of the titanic stellar blast disappearing into oblivion in the spiral galaxy NGC 2525, located 70 million light-years away.

Hubble began observing SN 2018gv in February 2018, after the supernova was first detected by amateur astronomer Koichi Itagaki a few weeks earlier in mid-January. Hubble astronomers were using the supernova as part of a program to precisely measure the expansion rate of the universe -- a key value in understanding the physical underpinnings of the cosmos. The supernova serves as a milepost marker to measure galaxy distances, a fundamental value needed for measuring the expansion of space.

In the time-lapse sequence, spanning nearly a year, the supernova first appears as a blazing star located on the galaxy's outer edge. It initially outshines the brightest stars in the galaxy before fading out of sight.

"No Earthly fireworks display can compete with this supernova, captured in its fading glory by the Hubble Space Telescope," said Nobel laureate Adam Riess, of the Space Telescope Science Institute (STScI) and Johns Hopkins University in Baltimore, leader of the High-z Supernova Search Team and the Supernovae H0 for the Equation of State (SH0ES) Team to measure the universe's expansion rate.

The type of supernova seen in this sequence originated from a burned-out star -- a white dwarf located in a close binary system -- that is accreting material from its companion star. When the white dwarf reaches a critical mass, its core becomes hot enough to ignite nuclear fusion, turning it into a giant atomic bomb. This thermonuclear runaway process tears the dwarf apart. The opulence is short-lived as the fireball fades away.

Because supernovae of this type all peak at the same brightness, they are known as "standard candles," which act as cosmic tape measures. Knowing the actual brightness of the supernova and observing its brightness in the sky, astronomers can calculate the distances of their host galaxies. This allows astronomers to measure the expansion rate of the universe. Over the past 30 years Hubble has helped dramatically improve the precision of the universe's expansion rate.

You could say Seattle came alive with more than an even flow of tourism dollars from a pair of highly-anticipated Pearl Jam concerts, according to rockin’ new research by West Virginia University economists.

Dubbed the “Home Shows,” two Pearl Jam concerts in August 2018 helped net the seaport city $58 million in additional hotel revenue and $9 million in hotel tax revenue. Compare that to Seattle Mariners baseball games, which generate $140,000 in additional hotel revenue on game days, and the researchers make a clear case for large, one-off events as economic boosters.

The study, “Why Go Home? Pearl Jam’s ‘Home Shows’ & Hotel Demand,” was authored by Joshua Hall, chair and professor of economics, and Justin Parker, a 2020 Ph.D. economics graduate. It was published in the Annals of Tourism Research Empirical Insights.

“While many events that attract visitors do not create large economic impacts (sports, for example) because a portion of the attendees are local and thus just represent spending that would happen anyway, events can generate large impacts under the right conditions,” Hall said. “The Pearl Jam ‘Home Shows’ seem to be the perfect conditions.

“Baseball games are primarily visited by local fans. While there will be some out-of-area visitors who stay overnight, our data show they are small and do not shift demand enough to lead to a large increase in room prices and thus hotel revenue and taxes. The key difference is not between a concert and Mariners games, rather it is between events that draw people in from far away – thus requiring hotel nights – and events that mostly draw locals.”

Hall believed the timing of the concert – at summer’s end in early August – combined with a planned off-day between the two shows made it ideal for loyal fans wanting to combine a live music experience with a vacation. The shows marked Pearl Jam’s first in Seattle – their hometown – in five years and attracted fans from across the globe.

Every Pearl Jam show is also different than the one prior, so fans attending both were guaranteed a unique opportunity from each performance.

Hall and Parker found that the concerts, held Aug. 8 and 10, increased average daily room rates by as much as $144 a night and hotel occupancy to more than 90 percent.

One contributor to the Seattle economy was Hall himself, who attended the concerts with his wife, Sabrina, as part of their 20th wedding anniversary. The couple flew from Clarksburg to Seattle via Chicago, and the plane from Clarksburg was full with everyone wearing Pearl Jam apparel, Hall said.

“Then when I checked into the hotel, I chatted with the manager,” he said. “He told me that room rates got up to over $400 a night and that he thought everyone in the hotel was a Pearl Jam fan based on their clothing when they checked in. That made me think – based on what I knew about their ticketing system – that this would be the ideal conditions for large economic impacts.

“In the stands I saw and met people from all over the country and world - many international fans bring their country’s flags to hold up - which further led me to realize that I wanted to estimate the impact of these shows on hotel demand and hotel tax revenue.”

Hall added that research like this can inform policymakers’ decisions regarding permitting and other forms of public support for concerts and cultural events.

By contrast, some sporting events do not result in economic boosts for host cities. The City of Charlotte spent $330,000 on public safety surrounding the 2017 PGA Championship, although the event had no significant impact on hotel revenue and taxes, according to one study. Meanwhile, the City of Seattle estimates each World Cup 2026 game hosted will cost $1.32 million for security. Hall projects the city will only be able to recoup those costs through the hotel tax if most attendees are from outside Seattle.

“Given the uniqueness of Pearl Jam the band and the ‘Home Shows,’ we argue that this case presents an upper bound of what an event designed to attract tourists can have on hotel demand,” Hall said. “Tourism, and consequently hotel demand, are a key component of the economic development strategy of many cities.”

Citation: “Why go home? Pearl Jam's ‘Home Shows’ & hotel demand”

Journal

Annals of Tourism Research Empirical Insights

More than 100 million infections of Zika virus within Central and South America and the Caribbean went undetected between 2015 and 2018, according to a new study.

The University of Notre Dame researchers who conducted the study, published in PLOS Neglected Tropical Diseases, said the results show a need for improvements to current infectious disease surveillance systems. The study also provides insight into the potential severity of future outbreaks and the current state of herd immunity of Zika in the West.

"Fewer than 1 percent of cases were actually reported and it shows our surveillance systems catch only a small percentage of actual infections," said Sean Moore, research assistant professor in the Department of Biological Sciences at Notre Dame and lead author of the study. "We need to think about how to improve surveillance systems to get a better sense of transmission, especially in cases of diseases that yield a high number of asymptomatic infections."

The first confirmed case of Zika in the Americas was reported in Brazil in 2015, with infection spreading rapidly, reaching as far north as Florida and Puerto Rico. In 2016 the World Health Organization (WHO) declared the epidemic a Public Health Emergency of International Concern.

The Pan American Health Organization, which serves as an international agency for the Americas and a regional office of the WHO, totaled symptomatic infections of Zika at more than 800,000 between 2015 and 2018 -- a number far below the results of the Notre Dame study. Moore's team estimated 132.3 million infections across Latin America and the Caribbean, having collected data from 15 countries and territories in South America, Central America and the Caribbean with a combined total population of 507.1 million.

"There are some similarities to the current situation with COVID-19," Moore said. "Between 20 and 50 percent of Zika infections are asymptomatic. Even when symptoms are present, they tend to be mild, so if the infection is not severe enough for an individual to seek medical attention, those cases can go undiagnosed."

Understanding the scope of underreporting is particularly important to gain an accurate sense of herd immunity in the region. Once infected, individuals who recover from Zika virus are believed to have lifelong immunity, Moore said. While cases have dropped substantially since 2018, a remaining concern is the potential for future outbreaks.

"Our research suggests a need for a better understanding of how much transmission is happening within a community," said Moore. "The risk of congenital birth defects in pregnant women infected with Zika virus required a separate surveillance system -- testing both the mother and the baby -- to capture a more accurate indicator of underlying transmission. Without widescale testing and a comprehensive system like that, we can miss how large an outbreak is in the general population."

A recent study co-authored by Moore and colleagues at Notre Dame found that gaps in surveillance and limited testing resulted in more than 100,000 coronavirus infections in the United States that went undetected in the early months of the pandemic.

Many marketing studies have examined the impact of direct-to-consumer advertising of pharmaceuticals on sales and market shares. But in a new study, a researcher from The University of Texas at Dallas wanted to know whether drug advertising might have some unintended, population-level health consequences.

"A colleague and I were brainstorming, and I wondered, 'Can Viagra ads result in more babies?'" said Dr. Tongil "TI" Kim, assistant professor of marketing in the Naveen Jindal School of Management and one of the study's co-authors. "With a more or less fixed gestation period, my colleague and I knew that we could compare advertising amount and birth rates after 10 months."

In the study, published online April 28 and in the August print issue of the Journal of Marketing Research, Kim and Dr. Diwas KC of Emory University explored the impact of direct-to-consumer advertising of erectile dysfunction (ED) drugs on birth rate at the population level.

The researchers examined local television commercials for three drug brands: Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). They compared advertising data with hospital data from Massachusetts between 2001 and 2010, and with 15 million birth certificate records from the U.S. between 2000 and 2004.

They used a type of quasi field experiment -- a way to show causality in economics and marketing -- to address many potential confounding factors. They examined two sets of adjacent rural ZIP codes with similar characteristics, where one side received more ED drug ads than the other side due to discontinuity in TV ad market delineation. In other words, they compared two sets of ZIP codes that are very similar in terms of demographics and socioeconomic factors except for the level of ED drug ads.

Additionally, the researchers considered other variables that might have affected increased birth rates during these time periods, such as inclement or cold weather. They also considered other advertising, over-the-air signal quality and the possibility of couples moving across the television markets' geographic borders, and determined those factors were not major concerns in the study's setting.

In further robustness checks, the researchers replaced ED drug advertising with advertising for an unrelated drug category and found no impact on birth rates. Also, they did not find significant effects in earlier months as gestation would take at least nine months.

The researchers found that in ZIP codes where more ED drug ads ran than in neighboring ZIP codes, the birth rates were higher 10 months after the advertising aired. Their results showed that a 1% increase in ED drug advertising contributed to an increase of 0.04% to 0.08% of total births. They also found the ads particularly increased births among families with children.

The researchers believe that some viewers watched the ads and purchased ED drugs to improve their chances of achieving pregnancy (consumption effect), while others may have been affected by the suggestive nature of the ads without purchasing ED drugs (media effect).

"As for the content of the ads, many of the ED drug commercials during the data period featured suggestive ad copy and content," Kim said, "which resulted in some people deeming ED drug ads inappropriate for family viewing, as demonstrated by a legislative bill that was introduced in 2009 calling to ban ED drug ads on TV between 6 a.m. and 10 p.m."

Further analysis using Google Trends data indicated that more frequent ED drug advertising was associated with higher pregnancy-intent keyword searches.

One popular hypothesis for the increased birth rates focused on older male ad viewers taking the pill and fathering more babies, Kim said. The data, however, did not show an increase in the average age of the fathers. It is possible this effect plays a role equally across different age groups, he said.

An unexpected finding was a stronger effect from the ads on birth rates in regions with lower incomes.

"It was surprising. During our data period, the majority of ED drug consumers paid the full price out of their own pockets because ED drugs were generally not covered by insurance in the U.S.," Kim said.

Based on the increased Google searches with intent to get pregnant and higher birth rates in lower-income areas that cannot be solely explained by the consumption effect, the researchers believe the media effect is possible.

"Can mere TV content affect fertility decisions? Many studies have found this. For example, the launch of TV shows in Brazil about female working professionals was linked to a substantial decrease in the nation's birth rates," Kim said.

The researchers said their study could provide companies a framework to monitor unintended health consequences in relation to the launch and marketing of pharmaceutical goods. Companies should be aware that, beyond simply increasing sales and market shares, marketing activities may have unforeseen spillover effects on societal outcomes, especially if the products are related to health or wellness.

"This is not only a responsible thing to do, but it can also create creative marketing opportunities," Kim said. "For example, companies selling infant-related medicines and goods like children's cold medicine, baby car seats or diapers might use ED drug ads as an additional market variable to better anticipate and predict local pregnancy rates 10 months later -- essentially their market potential -- and improve upon jointly deploying marketing and distribution resources across various regions."

The study also has implications for policymakers. Kim said they should be mindful of the multifaceted and even unexpected outcomes when considering whether to allow direct-to-consumer advertising of pharmaceuticals -- something that only is permitted in the U.S. and New Zealand. The Food and Drug Administration relaxed restrictions on direct-to-consumer advertising in 1997. Since then, TV advertising for pharmaceuticals increased substantially, with more than 80 drug ads estimated to be aired every hour on U.S. television.

Religious hospital policies that restrict reproductive health care are poorly understood by patients, according to a new study published Sept. 17 in AJOB Empirical Bioethics.

Researchers from the University of Chicago and the University of California, San Francisco found that women value clear information shared early from their health care providers to help them anticipate religious restrictions before their care becomes urgent.

Jocelyn Wascher, MD, an obstetrician-gynecologist resident at the University of Chicago Medicine, Debra Stulberg, MD, Chair of UChicago's Department of Family Medicine, and UCSF medical sociologist Lori Freedman, PhD, interviewed 33 reproductive-age women from a national survey sample who had sought care from a Catholic hospital. Most women identified as Christian or Catholic, and were diverse geographically, in age, and in racial and ethnic identity. The women expressed respect for the religious beliefs of the doctors and hospital administrators, but struggled to balance this with valuing personal autonomy and decision-making.

One woman interviewed by researchers needed a Cesarean-section delivery and wanted to have her tubes tied at the same time. However, she was told on the day of her C-section that the hospital did not perform tubal ligations due to its religious beliefs. She told researchers, "When you go to a hospital, you want them to do what you want them to do. You should be in charge of your own medical care and not their beliefs."

Other women in the study shared that sentiment, adding that patients should research hospital policies and affiliations before choosing where to receive care. However, they also wanted the hospital to make more effort to inform them.

The woman who was denied tubal ligations during her C-section said she was upset that the hospital didn't tell her about their rules beforehand. "I also feel that they could've told me sooner than the day of my C-section," the woman said.

Another interviewee told researchers that religious restrictions on care "need to be plastered in 50-foot neon letters at the front door of the building," rather than something a woman learns in real time if she happens to have a helpful physician.

The study's authors highlighted that the American Medical Association advises physicians who hold moral objections to specific services should disclose any objections prior to establishing a patient-physician relationship. They also recommend informing patients of all available treatment options, and referring them to other providers if necessary. The authors recommend that health care institutions be held to the same ethical standards.

"I've cared for numerous patients who were denied desired reproductive health care because of the religion of the hospital they happened to show up at," said Stulberg, who completed her residency at a hospital that transitioned from secular to Catholic during her time there.

Stulberg saw patients quickly lose access to contraception and pregnancy-related care. It spurred her interest in the topic and led her to pursue ethics training through UChicago's MacLean Center for Clinical Medical Ethics before joining the University's faculty. Today it's her primary research focus.

Wascher, the paper's first author, chose to be an OB-GYN in order to provide comprehensive care around pregnancy and reproductive health. "It's hard to imagine sitting with a patient who wants and would medically benefit from my care, and then having to tell her, 'I'm sorry, we can't do that here.' It would break my heart," she said.

Research from the University of Kent's School of Economics sheds new light on a long-standing obstacle to improving agricultural productivity in developing countries: the reluctance of small-scale farmers to adopt modern technologies because of the risks associated with them.

The paper, published in Science Direct, examined the relationship between attitudes towards risk among small-scale aquafarmers in Ghana and the time they take to adopt new technologies that reduce traditional risks, including; poor weather conditions, aquatic predators and poor hygiene.

The researchers conducted a series of psychological experiments with aquafarmers in 30 villages in four regions in southern Ghana to measure their aversion to risk and willingness to take gambles. They also recorded the aquafarmers' adoption of three innovative technologies recently introduced to Ghana: predator-proof floating cages for fish; a nutrient-rich fish feed; and a fast-growing, disease-resistant breed of tilapia fish.

Results showed that aversion to traditional production risks accelerated the adoption of all three technologies. However, adoption of floating cages was slower due to the significant upfront financial investment required, making small-scale experimentation with the technology impractical. The study also found that once aquafarmers in a community have started using the cages, the aversion by others to take the risk was further reduced.

Based on their findings, the study's authors advocate providing practical information about new agricultural technologies and information about positive returns from their adoption with the help and encouragement of regional extension agents to encourage the adoption of new agricultural technologies by small-scale farmers in developing countries.

Dr Adelina Gschwandtner, Senior Lecturer in Economics and Principle Investigator, said: 'These findings may have significant consequences beyond Africa and onto the global agricultural sector. Addressing traditional perceptions with this new understanding of the potential to reduce risk by adopting new ideas, methods, and technologies, may broaden how business ventures are viewed and conducted in the future. This in turn may help agricultural ventures in developing nations become secure and allow them to flourish.'

Researchers at Yale and elsewhere previously identified a host of genetic risk factors that help explain why some veterans are especially susceptible to the debilitating symptoms of post-traumatic stress disorder (PTSD).

A new Yale-led study published Oct. 1 in the journal Biological Psychiatry has now identified a social factor that can mitigate these genetic risks: the ability to form loving and trusting relationships with others.

The study is one of the first to explore the role of nurture as well as nature in its investigation of the biological basis of PTSD.

"We exist in a context. We are more than our genes," said Yale's Robert H. Pietrzak, associate professor of psychiatry and public health, and senior author of the study.

Pietrzak is also director of the Translational Psychiatric Epidemiology Laboratory of the Clinical Neurosciences Division of the U.S. Department of Veterans Affairs National Center for PTSD.

Like many genetic studies on mental disorders such as depression, anxiety, and schizophrenia, PTSD studies have revealed numerous genetic risk factors that contribute to the severity of the disorder. For instance, a previous study of more than 165,000 U.S. military veterans led by Yale's Joel Gelernter, the Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, found variants in eight separate regions of the genome that help predict who is most likely to experience the repeated disturbing memories and flashbacks that are hallmark symptoms of PTSD.

In the new study, Pietrzak, Gelernter, and colleagues looked at psychological as well as genetic data collected from the National Health and Resilience in Veterans Study, which surveyed a national sample of U.S. military veterans, and is supported by the National Center for PTSD. The researchers specifically focused on a measure of attachment style -- the ability or inability to form meaningful relations with others -- as a potential moderator of genetic risk for PTSD symptoms.

Individuals with a secure attachment style perceive relationships as stable, feel that they are worthy of love and trust, and are able to solicit help from others. Those with an insecure attachment style report an aversion to or anxiety about intimacy with others, and have difficulty asking for help from others.

They found that the ability to form secure attachments essentially neutralized the collective effects of genetic risk for PTSD symptoms. The impact was particularly pronounced in a variant of the IGSF11 gene, which has been linked to synaptic plasticity or the ability of the brain to form new connections between brain cells.

Pietrzak noted that deficits in synaptic plasticity have also been linked to PTSD, depression, and anxiety, among other mental disorders. The findings illustrate the importance of integrating environmental and social as well as genetic factors in the study of PTSD and related disorders, the authors said.

"Social environmental factors are critical to informing risk for PTSD and should be considered as potential moderators of genetic effects," he said. "The ability to form secure attachments is one of the strongest protective factors for PTSD."

The findings, which will help predict who is at greater risk of experiencing severe symptoms of PTSD, also suggest that psychological treatments targeting interpersonal relationships may help mitigate PTSD symptoms in veterans with elevated genetic risk for this disorder, he said.