Culture

High-resolution micro-CT scanning of the skull of the fossil specimen known as "Little Foot" has revealed some aspects of how this Australopithecus species used to live more than 3 million years ago.

The meticulous excavation, cleaning and scanning of the skull of the ~3.67 million-year-old fossil specimen has revealed the most complete Australopithecus adult first cervical vertebra yet found. A description of the vertebra by Wits University researchers Dr Amélie Beaudet and the Sterkfontein team was published in the Scientific Reports. This research program is supported by the the Centre of Excellence in Palaeosciences, Scientific Palaeontological Trust, National Research Foundation, University of the Witwatersrand and the French National Centre for Scientific Research through the French Institute of South Africa.

The first cervical vertebra (or atlas) plays a crucial role in vertebrate biology. Besides acting as the connection between the head and the neck, the atlas also plays a role in how blood is supplied to the brain via the vertebral arteries.

By comparing the atlas of "Little Foot" with other fossils from South and East Africa as well as living humans and chimpanzees, the Wits University team shows that Australopithecus was capable of head movements that differ from modern humans.

"The morphology of the first cervical vertebra, or atlas, reflects multiple aspects of an organism's life," says Beaudet, the lead author of the study. "In particular, the nearly complete atlas of 'Little Foot' has the potential to provide new insights into the evolution of head mobility and the arterial supply to the brain in the human lineage."

The shape of the atlas determines the range of head motions while the size of the arteries passing through the vertebrae to the skull is useful for estimating blood flow supplying the brain.

"Our study shows that Australopithecus was capable of head movements that differ from us. This could be explained by the greater ability of Australopithecus to climb and move in the trees. However, a southern African Australopithecus specimen younger than 'Little Foot' (probably younger by about 1 million years) may have partially lost this capacity and spent more time on the ground, like us today."

The overall dimensions and shape of the atlas of "Little Foot" are similar to living chimpanzees. More specifically, the ligament insertions (that could be inferred from the presence and configuration of bony tubercles) and the morphology of the facet joints linking the head and the neck all suggest that "Little Foot" was moving regularly in trees.

Because "Little Foot" is so well-preserved, blood flow supply to the brain could also be estimated for the first time, using evidence from the skull and vertebrae. These estimations demonstrate that blood flow, and thus the utilisation of glucose by the brain, was about three times lower than in living humans, and closer to the those of living chimpanzees.

"The low investment of energy into the brain of Australopithecus could be tentatively explained by a relatively small brain of the specimen (around 408cm3), a low quality diet (low proportion of animal products) or high costs of other aspects of the biology of Australopithecus (such as upright walking). In any case, this might suggest that the human brain's vascular system emerged much later in our history."

Currently we are facing a dementia epidemic, with estimations showing that by 2050 approximately 131 million people will be affected. Every 7 seconds a patient is diagnosed worldwide. Because the common forms of dementia occur in the elderly, delaying the onset or worsening of the cognitive impairment could translate into a significant reduction of the incidence of the disease. Estimations have shown that of the huge number of cases expected by 2050, roughly 23 million could be avoided if the onset of the disease could be delayed by 2 years. Despite the ambition to identify a disease modifying therapy or a cure for dementia by 2025 set by the G8 dementia summit in 2013, the findings so far are not very encouraging.

To date there is growing evidence of the association of vascular risk factors like hypertension, high cholesterol levels or diabetes mellitus with cognitive impairment and Alzheimer's disease. Unfortunately, simply managing these risk factors had little effect in reducing the incidence of dementia. These factors, however, strongly increase the risk of a patient to suffer an ischemic stroke and incident stroke approximately doubles the risk of dementia. From the study of Saver published in 2006 we know that "each hour in which treatment fails to occur the brain loses as many neurons as it does in 3.6 years of normal aging".

These neuronal losses occur through ischemic necrosis in the core of the infarction, but may be prolonged up to 2 weeks after the ischemic insult in the penumbral area surrounding the ischemic core through another type of cell loss, namely apoptosis. In initiating apoptosis oxidative species have a major role. Several authors have shown consistent increases in oxidative stress after an ischemic stroke. As the authors pointed out in a previous study, oxidative stress increases mainly after cardioembolic stroke, followed by lacunar stroke, with a less prolonged burst of generation of oxidative species following thrombotic stroke.

There is a considerable overlap between the oxidative stress-induced pathogenesis in ischemic stroke and Alzheimer's disease including mitochondrial dysfunction (the mitochondria being the main generators of energy in the cells), calcium overload of the cells, activation of different destructive enzymes by the excess intracellular calcium, aberrant gene transcription and expression, induction of autophagy (a process by which cells degrade their own cytoplasmic proteins and organelles) and activation of inflammatory responses.

Despite promising results of antioxidant molecules in animal models of ischemic stroke, human clinical trials were disappointing possibly due to late administration and incorrect selection of patients. However, in a study published in 2019, edaravone (an antioxidant molecule) given within 48 hours after endovascular revascularization in acute ischemic stroke was associated with greater functional independence at hospital discharge, lower in-hospital mortality and reduced intracranial hemorrhage after admission in a study which enrolled over 10,000 patients. More recently in a report presented at the International Stroke Conference 2020, nerinetide or NA1, a molecule which reduces endogenous nitric oxide (also an oxidative species) generated inside the cell during ischemia, improved the outcome of ischemic stroke patients who underwent endovascular thrombectomy. Unfortunately, NA1 interacted with alteplase, limiting its efficiency in patients who were also thrombolysed.

Antioxidants have been evaluated also in patients suffering from degenerative diseases, Alzheimer's disease included, with promising results in animal models but inconclusive results in clinical trials. Therapeutic strategies are hampered by the dual role of oxidative species in the organism. On one hand, increased ROS production contributes to age-related chronic conditions and on the other, oxidant species function as signaling molecules in pathways that are critical for cell survival. However, based on the compelling evidence of the implication of oxidative stress in AD pathogenesis and of the pivotal role of mitochondria, molecules acting as mitochondria-targeted antioxidants show promise in animal models of neurodegenerative diseases, improve mitochondrial function after coronary ischemia/reperfusion in rats, and some have already been developed into drugs used in clinical trials in type 2 diabetic patients.

In view of the implication of oxidative stress in the genesis of AD pathology, the authors hypothesize that with aging, in the presence of well-established vascular risk factors, and possibly with a genetic contribution, AD pathology develops slowly without clinically overt cognitive impairment. However, after a stroke there is a sudden burst in oxidative stress which accelerates the pathogenesis of dementia and leads to clinically obvious cognitive impairment. If this hypothesis would be proven the reason for reaching antioxidant treatment in acute ischemic stroke would be reinforced. Further studies in this direction with long follow-up periods would be needed. Nonetheless, in view of the high incidence and prevalence of the disease, the results could be rewarding.

Many foods - whether it's the mozzarella on your favorite pizza, the olive oil in salad dressing or hollandaise sauce during asparagus season - contain lots of fat. The fatty acids in these foods are among the essential nutrients that people need to survive. When someone eats more fatty acids than the body can immediately convert into energy, the extra amount is stored in tissues - often in the form of unwanted rolls of fat around the hips or stomach - and serves as a kind of reserve supply.

The quantity of fatty acids transported by blood to the tissues and deposited there is determined by a wide range of factors. Researchers at the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC) have now identified one of these factors as the protein EHD2.

If this protein is missing completely, fat-storing cells take up significantly more fatty acids from the cellular environment. Dr. Claudia Matthaeus first observed this phenomenon in the brown adipose tissue of mice during her work at the MDC. She finds it particularly exciting that EHD2 apparently plays a key role in human fat metabolism, too. "We have discovered that overweight people produce less EHD2 than people with normal weight," Matthaeus says. It is not clear yet why this is the case. Based on these new insights, Matthaeus and her colleagues, including researchers from the MDC research group led by Professor Oliver Daumke, assume that EHD2 controls a metabolic pathway that regulates fatty acid uptake in fat cells. This pathway is modified in obesity, the researchers write in the journal PNAS.

Cellular uptake of fat occurs when portions of the cell membrane pinch off

Oliver Daumke is long acquainted with EHD2. The structural biologist has been characterizing the structure and mechanimsm of this protein for more than ten years. As a membrane protein, EHD2 resides inside muscle and fat cells. During the inward folding of the cell envelope, small flask-shaped membrane structures called caveolae are formed. These invaginations either remain on the surface of the cell membrane or they pinch off and carry foreign material - such as fatty acids - into the cell. This process is known as endocytosis, Daumke explains. The researcher assumes that the EHD2 protein assembles into ring-like structures around the neck of the membrane vessel and thus stymies the pinch-off process. Daumke is convinced that if EHD2 is not present as a stabilizer, caveolae pinch off more frequently and the cell takes up more fat.

This is precisely what Matthaeus and her colleagues examined. The researchers worked with mice in which the EHD2 gene had been switched off. Using an electron microscope, Matthaeus observed that compared to normal mice, many more caveolae had become detached from the plasma membrane. She was also able to determine that fatty acid uptake was greater in cells lacking EHD2 and that the lipid droplets, which are intracellular accumulations of fat, were larger in these cells.

Obesity influences EHD2 production

Matthaeus asked herself if she would also be able to observe an influence of EHD2 on fat metabolism in humans. So she, together with a colleague from Leipzig University, studied tissue samples from men and women with different body weight. She quickly discovered that in people who were overweight (body mass index of 25 or higher), cells produce less EHD2 than in slim people. The researcher presumes that there is a correlation between frequent membrane pinch-off and the formation of fat depots. "During obesity, we observed that the number of caveolae and their detachment from the membrane get out of sync," Matthaeus says.

In November, Matthaeus left the MDC to take a position at the National Institutes of Health in the United States. There she plans to continue her research into caveolae and fat metabolism. "There are still many unanswered questions," Matthaeus says. She is now especially interested in investigating the transport of fatty acids within the cell and the formation of lipid droplets.

Joint research conducted by The Nature Conservancy and the Kunming Institute of Botany, Chinese Academy of Sciences calculated the carbon-storing power of global soils and showcased approaches like agroforestry designed to capitalise on untapped potential.

A critical, nature-based approach to mitigating climate change has been right at our feet all along, according to a new study revealing that soil represents up 25% of the total global potential for natural climate solutions (NCS) - approaches that absorb CO2 from the atmosphere and lock it into landscapes, including forests, croplands and peatlands.

Representing the first time soil's total global potential for carbon-mitigation across forests, wetlands, agriculture and grasslands together has been catalogued, the study - led by scientists from The Nature Conservancy alongside Conservation International, Woods Hole Research Centre, University of Aberdeen, Yale University and the Kunming Institute of Botany, Chinese Academy of Sciences (KIB/CAS) - provided a timely reminder in this critical 'super year' for nature not to neglect the power of soils and the many benefits these ecosystems can deliver for climate, wildlife and agriculture.

Published in the journal Nature Sustainability entitled "The role of soil carbon in natural climate solutions". the research also argued that a lack of clarity to date regarding the full scale of this opportunity and how to best capitalise on it has restricted investment.

"While momentum continues to build behind the role nature can play in the global response to climate change, soils have historically enjoyed less of the limelight as a 'natural climate solution' compared with, say, forests or mangroves. Our study is designed to redress this situation," said lead author Dr. Deborah Bossio, The Nature Conservancy's Lead Soil Scientist. "By highlighting the full carbon-mitigation potential of soils across a range of landscapes, but also - crucially - exploring practical mechanisms that already exist for accelerating the uptake of these comparatively untapped approaches, including their integration into burgeoning carbon markets. This is particularly important for agriculture sector, for which more effective management of soils represents the single biggest contribution this industry can make towards mitigating climate change."

"Soils and improved soil management have a tremendous potential to store carbon. Agroforestry, and more generally just including more trees in the agricultural landscape, has been shown to be one of the most important approaches to increasing soil organic carbon with substantial global mitigation potential. In addition, highlighting the complimentary beneficial impacts available from improved agricultural production practices aimed at improving soil health, both the increased on-farm bio-diversity and livelihood diversification can enhance farm and ecosystem resilience," said co-author Dr. Robert Zomer of the KIB/CAS.

Demonstrating that soil carbon represents up to 25% of total global NCS potential, the paper also estimated that 40% of this potential will be delivered by protecting existing soil carbon reserves, while 60% will come from rebuilding stocks depleted by practices such as over-intensive arable agriculture and the draining of peatlands.

Breaking these data down further, the researchers also showed the share of total NCS potential that soil represents across various, climate-critical landscapes - from a relatively diminutive 9% of forest mitigation potential, through 47% for agricultural lands and grasslands, right up to 72% of total carbon sequestration potential in wetland landscapes.

The study also showed that agroforestry systems can have significant positive impacts on soil organic carbon across specific geographies. Moreover, the majority of other soil carbon pathways tend to be "no regrets" practices that deliver soil fertility, climate resilience and provide other ecosystem services alongside climate mitigation.

"We already know that nature has a powerful role in mitigating runaway climate change," said Prof. XU Jianchu from KIB/CAS, who was not associated with the study. "This study showed the NCS provide pathways for sustainable development that have both climate mitigation and livelihood improvement potential. It is essential that soil health become a central pillar of agricultural production, not just for climate mitigation, but also for both environmental and food security."

Over-reliance by countries on artificial intelligence to tackle international migration and manage future migration crisis could lead to serious breaches of human rights, a new study warns.

AI can help states and international organisations prepare for large movements of people, and improve reception conditions. But it could also be used to reinforce unlawful practices, bar entry and allow for discrimination, the research says.

The study, published in the journal Migration Studies, highlights how AI has the potential to revolutionise the way states and international organisations seek to manage international migration, including by potentially predicting the next migration crisis.

AI technologies may be used to perform tasks including identity checks, border security and control, and analysis of data about visa and asylum applicants in a way which can cut costs and increase efficiency. This could make the process quicker and easier for migrants and asylum seekers. AI could also help countries to spot potential gaps in their reception facilities, adapting them to comply with their legal obligations under international human rights law.

However, the analysis suggests AI could be used by countries to put measures in place to prevent arrivals. This includes assisting targeted maritime interventions aiming at returning migrants and asylum-seekers to places where they may fear for their lives or freedom.

AI has been used already in Canada for algorithmic decision-making in immigration and asylum determination, and in Germany, where technologies such as face and dialect recognition for decision-making in asylum determination processes have been piloted.

In the European Union (EU), the revised Schengen Information System (SIS) will be using facial recognition, DNA, and biometric data to facilitate the return of migrants in an irregular situation. Swedish authorities have used 'migration algorithms' based on techniques such as machine learning to forecast future migration flows.

The research says the use of AI could amplify the "digital divide" between states with more advanced technological capabilities and those lacking them. AI technologies could cement the leading position of those AI-capable states such as those in the global North, which would be placed at the forefront of the global efforts to manage migration in the years to come. States with less advanced technological means could be further isolated. This could lead to AI reinforcing a North verses South divide, unless southern countries develop their AI capabilities.

Dr Ana Beduschi, from the University of Exeter Law School and Institute for Data Science and Artificial Intelligence, who carried out the research, said: "AI is at risk of becoming another political tool, used to reinforce old state practices, aiming to curb international migration and prevent asylum-seekers from reaching their territories".

"AI technology may bring innovation, reduce costs, and build more effective systems for international migration management. However, it is important that such tools are developed and deployed within ethical and legal frameworks, in particular international human rights law."

The study recommends organisations and countries using AI should ensure the technology will not be detrimental to migrants' and asylum-seekers' rights.

New insight on what happens in brain cells to cause tremors in mice has been published today in the open-access journal eLife.

Uncontrollable movements called tremors are common and debilitating, but scientists have previously struggled to pinpoint their exact cause. The new study reveals the neural activity behind tremors, and suggests that targeting deep brain stimulation (DBS) to the cerebellum can help treat the condition. DBS is a technique used to treat movement disorders in patients who do not respond well enough to medications.

"While abnormalities in different brain cells in the cerebellum, particularly Purkinje cells, have previously been associated with tremors, it wasn't certain if and how Purkinje cells cause this condition," says lead author Amanda Brown, a graduate student in the Department of Neuroscience at Baylor College of Medicine in Houston, Texas, US.

To investigate this further, Brown and her colleagues studied mice with Purkinje cells that were unable to signal correctly. They then treated the mice with a drug that usually causes tremors and found that the animals did not develop the condition.

Next, they administered the drug to healthy mice and measured what happened in their Purkinje cells. They found that the animals' tremors coincided with abnormal bursts of activity in these cells. Using a technique called optogenetics, the team recreated these abnormal bursts in the Purkinje cells in untreated, healthy mice and found that this also led to tremors.

Finally, they showed that targeting DBS to the cerebellum where Purkinje cells are located could stop tremors in mice treated with the tremor-inducing drug. "DBS that targets part of the brain called the thalamus, which receives messages from the cerebellum, is already used to treat movement disorders in people," Brown explains. "But these findings highlight the cerebellum as a more direct potential target."

"Our study hints at a potential treatment option to reduce or curb tremors and other movement disorders involving the cerebellum," adds senior author Roy Sillitoe, Associate Professor of Pathology at Baylor College of Medicine. "Our next step is to explore whether cerebellar deep brain stimulation works as well in humans with tremors as in mice."

BUFFALO, N.Y. -- Need to reduce high-pitched noises? Science may have an answer.

In a new study, theoretical physicists report that materials made from tapered chains of spherical beads could help dampen sounds that lie at the upper range of human hearing or just beyond.

The impacts of such noises on health are uncertain. But some research suggests that effects could include nausea, headaches, dizziness, impaired hearing or other symptoms.

"There is a fair amount of ultrasonic stuff around us, and much of it has effects that are unknown. In warmer areas, you have pest control systems that are strongly reliant on ultrasonic emissions to drive out the pests. You have ultrasonics from machinery, from drilling. Certain lamps may emit these high-frequency noises," says Surajit Sen, PhD, professor of physics in the University at Buffalo College of Arts and Sciences. "What does it do to our hearing? And in return, what does it do to our brain?

"Because of these unknowns, we thought it would be of potential value to design a system that kills off high-frequency sound."

The new research appears in the February 2020 volume of Granular Matter and was published online in the journal in November 2019.

Sen co-authored the study with Luís Paulo Silveira Machado, PhD, professor of physics at the Federal University of Pará in Brazil. Machado did part of the work as a visiting scholar at UB with the financial support of his home university, and Sen's research was partially supported by a Fulbright-Nehru Academic and Professional Excellence Fellowship.

The study used computational modeling to explore how well various materials would dampen incoming sounds with frequencies up to 20 kilohertz -- high enough that only some people can hear these noises.

Machado and Sen researched a number of materials, all made from spherical beads of varying sizes surrounded by plastic walls.

The best set-up they found consisted of tapered chains of beads made from a metal called tungsten carbide, alternating with tapered chains of beads made from a plastic called Delrin. In computer simulations, this system effectively helped to filter high-frequency noises of varying loudness, greatly reducing these sounds.

The scientists have not yet tested the material in the laboratory. But if it works, the noise-filtering system could be used in headphones or other barriers that dampen high-frequency sound, the researchers say.

"An advantage of the proposed device is its simple configuration: spherical beads properly confined and positioned," Machado says. "This proposal allows a prototype of easy construction, with low cost and little maintenance. In addition, its configuration is scalable, being adaptable for small or large volumes. Our next step is to redirect the output signals, which is under study."

Largest microarray patch clinical vaccination study ever performed

First clinical microarray patch study to show dose sparing against standard intramuscular injection with comparable immune responses at a 1/6 dose

HD-MAP immune response significantly higher, faster than by IM injection at comparable doses

Vaccine on HD-MAP shown to be stable for 12 months at temperatures as high as 40oC

Cambridge, Mass., USA, and Brisbane, Queensland, Australia - March 17, 2020 (USA)/March 18, 2020 (Australia) - Vaxxas, a clinical-stage biotechnology company commercializing a novel vaccination platform, today announced the publication in the journal PLoS Medicine of groundbreaking clinical research indicating the broad immunological and commercial potential of Vaxxas' novel high-density microarray patch (HD-MAP). Using influenza vaccine, the clinical study of Vaxxas' HD-MAP demonstrated significantly enhanced immune response compared to vaccination by needle/syringe. This is the largest microarray patch clinical vaccine study ever performed.

In addition, using the HD-MAP, a 2.5 μg dose (1/6 of the standard dose) induced immune responses comparable to those induced by a standard dose of 15 μg injected IM, validating the dose-sparing potential of Vaxxas platform. In situations such as response to a pandemic, smaller doses could enable many more patients to be vaccinated by HD-MAP than by IM injection from a limited available volume of vaccine.

At higher doses of 10 and 15 μg, HD-MAP produced significantly high titers and faster onset kinetics than 15 μg injected IM (the standard dose). The CDC estimates that each year as many as 500,000 deaths occur due to influenza globally, and that in the United States, average mortality associated with influenza is more than 37,000 people for each year since 2010. Faster immune response achieved from the HD-MAP provides the potential to establish protection from infection in days instead of weeks, a significant public health benefit that could be extremely important for both seasonal and pandemic influenzas. In addition, higher overall immune responses provide the potential for disease protection that could span the duration of the annual flu season.

"We are extremely excited to publish these compelling clinical results showing the potential of our proprietary vaccination platform to deliver vaccines safely and effectively - including at lower doses -- than conventional approaches," said David L. Hoey, President and CEO of Vaxxas. "Microarray patches - like Vaxxas' HD-MAP - have long been viewed as having game-changing potential by targeting the active immune cells in the skin. With the significant demonstrated immune responses in this study, Vaxxas' HD-MAP is the first-ever needle-free platform to clinically validate such a compelling immunological profile."

In the journal article published in PLoS Medicine, the vaccine HD-MAP was stable when stored at 40°C (104°F) for at least 12 months, providing the potential for easy distribution without the cost and complexity of continuous refrigeration. Furthermore, the company is currently performing a clinical study in which self-administration of the HD-MAP is being studied. The combination of these features could be extremely beneficial, subject to regulatory approval, in situations such as annual seasonal influenza vaccinations and pandemic response to prevent the need for populations to congregate to have a vaccine administered.

"With vaccine coated onto Vaxxas HD-MAPs shown to be stable for up to a year at 40°C, we can offer a truly differentiated platform with a global reach, particularly into low and middle income countries or in emergency use and pandemic situations," said Angus Forster, Chief Development and Operations Officer of Vaxxas and lead author of the PLoS Medicine publication. "Vaxxas' HD-MAP is readily fabricated by injection molding to produce a 10 x 10 mm square with more than 3,000 microprojections that are gamma-irradiated before aseptic dry application of vaccine to the HD-MAP's tips. All elements of device design, as well as coating and QC, have been engineered to enable small, modular, aseptic lines to make millions of vaccine products per week."

The PLoS publication reported results and analyses from a clinical study involving 210 clinical subjects. The clinical study was a two-part, randomized, partially double-blind, placebo-controlled trial conducted at a single Australian clinical site. The clinical study's primary objective was to measure the safety and tolerability of A/Singapore/GP1908/2015 H1N1 (A/Sing) monovalent vaccine delivered by Vaxxas HD-MAP in comparison to an uncoated Vaxxas HD-MAP and IM injection of a quadrivalent seasonal influenza vaccine (QIV) delivering approximately the same dose of A/Sing HA protein. Exploratory outcomes were: to evaluate the immune responses to HD-MAP application to the forearm with A/Sing at 4 dose levels in comparison to IM administration of A/Sing at the standard 15 μg HA per dose per strain, and to assess further measures of immune response through additional assays and assessment of the local skin response via punch biopsy of the HD-MAP application sites. Local skin response, serological, mucosal and cellular immune responses were assessed pre- and post-vaccination.

LAWRENCE -- When a partial fossil specimen of a primordial marine worm was unearthed in Utah in 1969, scientists had a tough go identifying it. Usually, such worms are recognized and categorized by the arrangement of little knobs on their plates. But in this case, the worm's plates were oddly smooth, and important bits of the worm were missing altogether.

Discouraged, researchers placed the mystery worm in a "wastebasket" genus called Palaeoscolex, and interest in the lowly critter waned for the next 50 years.

That all changed recently when Paul Jamison, a teacher from Logan, Utah, and private collector, and his student Riley Smith were hunting fossils in the Spence Shale in Utah, a 506-million-year-old geologic unit housing a plethora of exceptionally preserved soft-bodied and biomineralized fossils. (Paleontologists call such a mother lode of fossils a "Lagerstätte.") There, Smith discovered a second, more thoroughly preserved example of the worm.

Eventually, thanks to Jamison's donation, the new fossil specimen arrived at the University of Kansas Biodiversity Institute, where Anna Whitaker, a graduate student in museum studies, researched and analyzed the worm with scanning electron microscopes, energy-dispersive X-ray spectrometry and optical microscopy.

At last, Whitaker determined the worm represented a new genus of Cambrian sea worm heretofore unknown to science. She's the lead author of a description of the worm just published in the peer-reviewed paleontological journal PalZ.

"Before the new species that we acquired there was only one specimen known from the Spence Shale," she said. "But with our new specimen we discovered it had characteristics that the original specimen didn't have. So, we were able to update that description, and based on these new characteristics -- we decided it didn't fit in its old genus. So, we moved it to a new one."

Whitaker and her colleagues -- Jamison, James Schiffbauer of the University of Missouri and Julien Kimmig of KU's Biodiversity Institute -- named the new genus Utahscolex.

"We think they're closely related to priapulid worms that exist today -- you can find them in the oceans, and they are very similar to priapulids based on their mouth parts," Whitaker said. "What's characteristic about these guys is that they have a proboscis that can evert, so it can turn itself inside out and it's covered with spines -- that's how it grabs food and sucks it in. So, it behaved very similarly to modern priapulid worms."

While today, Utah is not a place you'd look for marine life, the case was different 506 million years ago, when creatures preserved in the Spence Shale were fossilized.

"The Spence Shale was a shelf system, and it's really interesting because it preserves a lot of environments -- nearshore to even deeper offshore, which is kind of unusual for a Lagerstätte, and especially during the Cambrian. These animals were living in kind of a muddy substrate. This worm was a carnivore, so it was preying on other critters. But there would have been whole diversity of animals -- sponges, and trilobites scuttling along. We have very large, for the time, bivalve arthropods that would be predators. The Spence has a very large diversity of arthropods. It would have looked completely alien to us today."

Whitaker hopes to complete her master's degree this spring, then to attend the University of Toronto to earn her doctorate. The description of Utahscolex is Whitaker's first academic publication, but she hopes it won't be her last. She said the opportunity to perform such research is a chief reason for attending KU.

"I came for the museum studies program," she said. "It's one of the best in the country, and the program's flexibility has allowed me to focus on natural history collections, which is what I hopefully will have a career in, and also gain work experience in the collections and do research -- so it's kind of everything I was looking for in the program."

While ancient sea worms could strike many as a meaninglessly obscure subject for such intense interest and research, Whitaker said filling in gaps in the fossil record leads to a broader understanding of evolutionary processes and offers more granular details about the tree of life.

"I know some people might say, 'Why should we care about these?'" she said. "But the taxonomy of naming all these species is really an old practice that started in the 1700s. It underpins all the science that we do today. Looking at biodiversity through time, we have to know the species diversity; we have to know as correctly as we can how many species there were and how they were related to each other. This supports our understanding of -- as we move into bigger and bigger, broader picture -- how we can interpret this fossil record correctly, or as best we can."

CAMBRIDGE, MA -- MIT and Harvard University chemists have discovered the structure of an unusual bacterial enzyme that can break down an amino acid found in collagen, which is the most abundant protein in the human body.

The enzyme, known as hydroxy-L-proline dehydratase (HypD), has been found in a few hundred species of bacteria that live in the human gut, including Clostridioides difficile. The enzyme performs a novel chemical reaction that dismantles hydroxy-L-proline, the molecule that gives collagen its tough, triple-helix structure.

Now that researchers know the structure of the enzyme, they can try to develop drugs that inhibit it. Such a drug could be useful in treating C. difficile infections, which are resistant to many existing antibiotics.

"This is very exciting because this enzyme doesn't exist in humans, so it could be a potential target," says Catherine Drennan, an MIT professor of chemistry and biology and a Howard Hughes Medical Institute Investigator. "If you could potentially inhibit that enzyme, that could be a unique antibiotic."

Drennan and Emily Balskus, a professor of chemistry and chemical biology at Harvard University, are the senior authors of the study, which appears today in the journal eLife. MIT graduate student Lindsey Backman and former Harvard graduate student Yolanda Huang are the lead authors of the study.

A difficult reaction

The HypD enzyme is part of a large family of proteins called glycyl radical enzymes. These enzymes work in an unusual way, by converting a molecule of glycine, the simplest amino acid, into a radical -- a molecule that has one unpaired electron. Because radicals are very unstable and reactive, they can be used as cofactors, which are molecules that help drive a chemical reaction that would otherwise be difficult to perform.

These enzymes work best in environments that don't have a lot of oxygen, such as the human gut. The Human Microbiome Project, which has sequenced thousands of bacterial genes from species found in the human gut, has yielded several different types of glycyl radical enzymes, including HypD.

In a previous study, Balskus and researchers at the Broad Institute of MIT and Harvard discovered that HypD can break down hydroxy-L-proline into a precursor of proline, one of the essential amino acids, by removing the hydroxy modification as a molecule of water. These bacteria can ultimately use proline to generate ATP, a molecule that cells use to store energy, through a process called amino acid fermentation.

HypD has been found in about 360 species of bacteria that live in the human gut, and in this study, Drennan and her colleagues used X-ray crystallography to analyze the structure of the version of HypD found in C. difficile. In 2011, this species of bacteria was responsible for about half a million infections and 29,000 deaths in the United States.

The researchers were able to determine which region of the protein forms the enzyme's "active site," which is where the reaction occurs. Once hydroxy-L-proline binds to the active site, a nearby glycine molecule forms a glycyl radical that can pass that radical onto the hydroxy-L-proline, leading to the elimination of the hydroxy group.

Removing a hydroxy group is usually a difficult reaction that requires a large input of energy.

"By transferring a radical to hydroxy-L-proline, it lowers the energetic barrier and allows for that reaction to occur pretty rapidly," Backman says. "There's no other known enzyme that can perform this kind of chemistry."

New drug target

It appears that once bacteria perform this reaction, they divert proline into their own metabolic pathways to help them grow. Therefore, blocking this enzyme could slow down the bacteria's growth. This could be an advantage in controlling C. difficile, which often exists in small numbers in the human gut but can cause illness if the population becomes too large. This sometimes occurs after antibiotic treatment that wipes out other species and allows C. difficile to proliferate.

"C. difficile can be in your gut without causing problems -- it's when you have too much of it compared to other bacteria that it becomes more problematic," Drennan says. "So, the idea is that by targeting this enzyme, you could limit the resources of C. difficile, without necessarily killing it."

The researchers now hope to begin designing drug candidates that could inhibit HypD, by targeting the elements of the protein structure that appear to be the most important in carrying out its function.

ITHACA, N.Y. - When you smell an orange, the scent is most likely combined with several others: car exhaust, garbage, flowers, soap. Those smells bind simultaneously to the hundreds of receptors in your brain's olfactory bulb, obscuring one another, yet you can still recognize the smell of an orange, even when it's blended with a totally different pattern of other scents.

The precise mechanics of how mammals learn and identify smells have long eluded scientists. New Cornell research explains some of these functions through a computer algorithm inspired by the mammalian olfactory system. The algorithm both sheds light on how the brain works and, applied to a computer chip, rapidly and reliably learns patterns better than existing machine learning models.

"This is a result of over a decade of studying olfactory bulb circuitry in rodents and trying to figure out essentially how it works, with an eye towards things we know animals can do that our machines can't," said Thomas Cleland, professor of psychology and senior author of "Rapid Learning and Robust Recall in a Neuromorphic Olfactory Circuit," which published in Nature Machine Intelligence March 16.

"We now know enough to make this work. We've built this computational model based on this circuitry, guided heavily by things we know about the biological systems' connectivity and dynamics," Cleland said. "Then we say, if this were so, this would work. And the interesting part is that it does work."

Cleland and co-author Nabil Imam, Ph.D. '14, a researcher at Intel, applied the algorithm to an Intel computer chip. The research chip, known as Loihi, is neuromorphic - meaning it's inspired by the way the brain functions, incorporating digital circuits that mimic the way neurons communicate and learn. For example, the Loihi research chip is based on many parallel cores which communicate via discrete spikes, and the effects delivered by each of these spikes can change based solely on local activity. This architecture requires fundamentally different strategies for algorithm design compared with existing computer chips.

Using neuromorphic computer chips, machines could learn to identify patterns or perform certain tasks a thousand times faster than by using the computer's central or graphics processing units, as most programs do. Running certain algorithms on the Loihi research chip also uses about a thousand times less power than traditional methods, according to Intel.

The chip is the optimal platform for Cleland's algorithm, which can accept input patterns from an array of sensors, learn multiple patterns rapidly and sequentially, and then identify each of these meaningful patterns despite strong sensory interference. The algorithm can successfully identify odors even when their pattern is 80% different from the pattern the computer originally learned.

"The pattern of the signal has been substantially destroyed," Cleland said, "and yet the system is able to recover it."

The mammalian brain is stunningly adept at identifying and remembering smells, with hundreds or even thousands of olfactory receptors and complex neural networks rapidly analyzing the patterns associated with odors. Our brains also retain what we've learned even after we've acquired new knowledge - something that's easy for mammals but difficult for artificial intelligence systems. Particularly in deep learning approaches, everything must be presented to the network at the same time, because new information can distort or destroy what the system learned before.

The brain-inspired algorithm solves this problem, Cleland said.

"When you learn something, it permanently differentiates neurons," he said. "When you learn one odor, the interneurons are trained to respond to particular configurations, so you get that segregation at the level of interneurons. So on the machine side, we just enhance that and draw a firm line."

It also explains a previously misunderstood phenomenon: why the olfactory bulb of the brain is one of the few places where mammals can create new neurons after they've reached adulthood.

"The computational model turns into a biological hypothesis for why adult neurogenesis is important," Cleland said. "Because it does this thing that otherwise would make the system not work. So in that sense, the model is feeding back into biology. And in this other sense, it's the basis for a set of devices for artificial olfactory systems that can be constructed commercially."

The brain's complexity motivated Cleland to focus his neuroscience research around a theoretical approach guided by explicit computational models.

"When you start studying a biological process that becomes more intricate and complex than you can just simply intuit, you have to discipline your mind with a computer model," he said. "You can't fuzz your way through it. And that led us to a number of new experimental approaches and ideas that we wouldn't have come up with just by eyeballing it."

NEW YORK, NY (March 16, 2020) - CRISPR-based genetic screens have helped scientists identify genes that are key players in sickle-cell anemia, cancer immunotherapy, lung cancer metastasis, and many other diseases. However, these genetic screens are limited in scope: They can only edit or target DNA. For many regions of the human genome, targeting DNA may not be effective, and other organisms, such as RNA viruses like coronavirus or flu, cannot be targeted at all with existing DNA-targeting CRISPR screens.

Now, in an important new resource for the scientific community published today in Nature Biotechnology, researchers in the lab of Neville Sanjana, PhD, at the New York Genome Center and New York University have developed a new kind of CRISPR screen technology to target RNA.

The researchers capitalized on a recently characterized CRISPR enzyme called Cas13 that targets RNA instead of DNA. Using Cas13, they engineered an optimized platform for massively-parallel genetic screens at the RNA level in human cells. This screening technology can be used to understand many aspects of RNA regulation and to identify the function of non-coding RNAs, which are RNA molecules that are produced but do not code for proteins.

By targeting thousands of different sites in human RNA transcripts, the researchers developed a machine learning-based predictive model to expedite identification of the most effective Cas13 guide RNAs. The new technology is available to researchers through an interactive website and open-source toolbox to predict guide RNA efficiencies for custom RNA targets and provides pre-designed guide RNAs for all human protein-coding genes.

"We anticipate that RNA-targeting Cas13 enzymes will have a large impact on molecular biology and medical applications, yet little is known about guide RNA design for high targeting efficacy," said Dr. Sanjana, senior author of the study. "We set about to change that through an in-depth and systematic study to develop key principles and predictive modeling for most effective guide design."

Dr. Sanjana is a Core Faculty Member at the New York Genome Center, an Assistant Professor of Biology at New York University, and an Assistant Professor of Neuroscience and Physiology at NYU School of Medicine.

Cas13 enzymes are Type VI CRISPR (clustered regularly interspaced short palindromic repeats) enzymes that have recently been identified as programmable RNA-guided, RNA-targeting proteins with nuclease activity that allows for target gene knockdown without altering the genome. This property makes Cas13 a potentially significant therapeutic for influencing gene expression without permanently altering genome sequence.

"This is the kind of technology innovation that we foster and develop at the New York Genome Center. This latest CRISPR technology from the Sanjana Lab has exciting implications to advance the fields of genomics and precision medicine," said Tom Maniatis, PhD, Evnin Family Scientific Director and Chief Executive Officer, New York Genome Center.

Postdoctoral scientist Hans-Hermann Wessels and PhD student Alejandro Méndez-Mancilla, who are co-first authors of the study, developed a suite of new Cas13-based tools and conducted a transcript tiling and permutation screen in mammalian cells. In total, the researchers gathered information for more than 24,000 RNA-targeting guides.

"We tiled guide RNAs across many different transcripts, including several human genes where we could easily measure transcript knock-down via antibody staining and flow cytometry," said Dr. Wessels. "Along the way, we uncovered some interesting biological insights that may expand the application of RNA-targeting Cas13 enzymes." Among the team's findings, for example, are insights about which regions of the guide RNA are more important for recognition of a target RNA. Using thousands of guide RNAs with 1, 2 or 3 single-letter mismatches to their target RNA, they identified a critical "seed" region that is exquisitely sensitive to mismatches between the CRISPR guide and the target. This discovery will aid scientists in designing guide RNAs to avoid off-target activity on unintended target RNAs. Since a typical human cell expresses approximately 100,000 RNAs, accurate targeting of Cas13 of only the intended target is vital for screening and therapeutic applications.

In addition to furthering our understanding of Cas13 off-targets, the "seed" region could be used for next-generation biosensors that can more precisely discriminate between closely related RNA species. In total, this study increases the number of data points from previous Cas13 studies in mammalian cells by more than two orders of magnitude.

"We are particularly excited to use the optimized Cas13 screening system to target noncoding RNAs," said fellow co-first-author Méndez-Mancilla. "This greatly expands the CRISPR toolbox for forward genetic and transcriptomic screens." In the study, the researchers noticed a marked difference in protein knockdown when targeting different protein-coding and non-coding elements of messenger RNAs, and found evidence that Cas13 competes with other RNA-binding proteins involved in transcript processing and splicing.

The team recently leveraged their guide RNA predictive model for a particularly critical analysis: The COVID-19 public health emergency is due to a coronavirus, which contains an RNA - not DNA - genome. Using the model derived from their massively-parallel screens, the researchers have identified optimal guide RNAs that could be used for future detection and therapeutic applications. Predictions for Cas13 guide RNAs for a strain of SARS-CoV-2 isolated in New York have been made available online at: http://bit.ly/coronavirus-guides

Read more about the study at: https://www.nature.com/articles/s41587-020-0456-9. The web tool for predictive scoring of Cas13 guide RNAs can be found at http://cas13design.nygenome.org. Other coauthors on the study include, Mateusz Legut, PhD, and Zharko Daniloski, PhD, and NYU Biology PhD student Xinyi Guo.

Children's museums can be a challenging environment for parents who feel the urge to explain the science behind all the novel activities that dazzle youngsters.

Sometimes that impulse goes awry, as when a well-meaning parent offers a detailed explanation that interrupts a youngster's exploration and dampens the fun--and the learning.

New research suggests that timing is key to supporting children's learning in these environments.

The best way to engage with children is to listen to them, watch what they are doing, and offer explanations as the child is beginning to explore an exhibit--not before or after, according to a team of researchers at the University of California, Santa Cruz; the University of Texas, Austin; and Brown University.

"For parents, it's important to be sensitive to the child's actions and choose your moment to jump in," said Maureen Callanan, a professor of psychology at UC Santa Cruz.

Callanan, a specialist in child development, has spent decades observing parent-child interactions at children's museums to better understand how children learn in "informal" learning environments. Children learn both from exploring on their own and from hearing their parents' explanations, but the latest evidence indicates that learning is enhanced when parents time their offerings with what Callanan calls children's "emerging exploration."

"We did find this very precise pattern," she noted. "It's the Goldilocks moment--not too early and not too late. Stepping up at just the right moment is key to helping children learn and figure things out."

The results of this NSF-funded research appear in Monographs of the Society for Research in Child Development, coauthored by Callanan; Cristine Legare, associate professor of psychology at UT-Austin; David Sobel, a professor of cognitive, linguistic, and psychological sciences at Brown University; a team of postdoctoral, graduate, and undergraduate students; and museum partners at the three museums where the research took place: Children's Discovery Museum of San Jose, Thinkery in Austin, TX, and Providence Children's Museum in Rhode Island.

A natural laboratory for studying early science learning

Children's museums are the perfect environment in which to explore the delicate balance between "explaining and exploring," because researchers have access to everyday conversations among families in a setting designed to foster early science learning.

"A lot of Western parents assume we have to teach things to our kids, while a lot of museum staffers think exploring is more important and that parents shouldn't lecture at their kids," said Callanan. "Really, it's neither all exploration or all explanation. It's a combination that best supports children's learning."

Museums, parents, and schools are eager to support children's curiosity and their STEM learning, so understanding how to integrate explaining and exploring can lead to better museum exhibits, more learning in museums and schools, and more productive interactions between parents and children.

"These insights about the give-and-take between parents and children are valuable, and they underscore the benefits of these museum-university collaborations," said Jenni Martin, director of education at the Children's Discovery Museum. "These findings help us do our job better, and the ultimate beneficiaries are children."

The museum has partnered with Callanan for more than 25 years in the study of how young children learn to reason about cause and effect--an important element of thinking about science. Previous research has focused on talk--the kinds of "why" questions children ask, when they pose questions, and how parents explain things. Other research has focused on exploratory play.

"Explaining and exploring are both happening all the time," said Callanan. "Sometimes we make judgments about which one is 'better'--some people think it's better for kids to figure out things for themselves. But that leaves out lots of things that are difficult to learn through hands-on exploring."

Which is why Callanan and her colleagues wanted to investigate what happens when children are playing with objects--in this case, gear exhibits at the three museums--and talking with their parents. "We wanted to see if there were patterns of how explaining and exploring work together, and how those patterns might vary across different families," she said.

Overall, the team found stronger links between exploring and understanding than between explaining and understanding, but the best predictor of understanding was when parents' explanations were linked closely with children's exploring.

"It's an indirect link, but it looks like that's the sequence--a little exploring, then a little explaining leads to deeper exploring and better understanding," said Callanan.

New Rochelle, NY, March 16, 2020--Physicians describe the standardized procedure of surgical anesthesia for patients with COVID-19 infection requiring emergency surgery to minimize the risk of virus spread and reduce lung injury in a Letter to the Editor published in Surgical Infections, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. Click here to read the full-text article free on the Surgical Infections website through April 16, 2020.

Xianjie Wen and Yiqun Li, the First Affiliated Hospital of Jinan University, Guangzhou, and the Second People's Hospital of Foshan City, China, coauthored the letter entitled "Anesthesia Procedure of Emergency Operation for Patients with Suspected or Confirmed COVID-19." The authors discuss the need for a negative pressure operating room, protection for the anesthesiologists, and special requirements for the anesthetic equipment, appliances, and drugs used. They describe the induction of anesthesia and the mechanical ventilation strategy during anesthesia maintenance to reduce ventilator-related lung injury.

"Avoiding airborne droplets from infected patients that are being ventilated is important to avoid transmission of these infections to OR personnel and other patients receiving care in the OR," says Surgical Infections Editor-in-Chief Donald E. Fry, MD, Northwestern University Feinberg School of Medicine, Chicago, IL.

A new paper including research from a Utah State University scientist provides a framework for understanding how light and noise pollution affects wildlife. The framework is the product of an effort among worldwide experts in ecology and physiology and reveals the presence of "sensory danger zones," or areas where sensory pollutants influences animal activity. The study is published in the journal Nature Ecology and Evolution. The paper is a collaborative work with principal investigator Neil Carter, assistant professor at the School for Environment and Sustainability. "From a conservation biology point of view, we don't know how to mitigate the effects of sensory pollution if we don't know what the pathway of harm is," said Carter.

"Although these results have consequences for imperiled species of conservation concern, they also suggest ways by which we may use light and sound for managing urban wildlife, mitigating wildlife-vehicle collisions, or preventing agricultural damage." said David Stoner, a research assistant professor in the Quinney College of Natural Resources at USU.

In their study, the authors give an example of New York City's annual 9/11 memorial tribute. The tribute coincides with birds' annual migration from northern regions to wintering grounds in Latin America. Because birds use "celestial cues" during their migration, the 44 spotlights that form two pillars of light can attract up to 15,000 birds in a single night.

"(The birds) will fly in circles inside the beams until morning, often dying from exhaustion and collisions with artificially lit structures," according to Carter and co-lead authors Davide Dominoni, a researcher of biodiversity, animal health and comparative medicine at the University of Glasgow; and Wouter Halfwerk, assistant professor in the Department of Ecological Science at VU Amsterdam University.

Both light pollution and traffic noise can mimic natural stimuli. For example, artificial lights cover the glow of the moon, preventing birds or insects from detecting it, or traffic noise can mask the audio spectral frequency of bird song, the researchers say.

These pollutants can also redirect an animal's attention away from its task: a cougar hunting deer can be distracted by headlights or road noise.

"If we understand the mechanism at play, perhaps we can devise specific interventions and solutions to adopt to minimize the effect of anthropogenic impacts," Dominoni said. "For instance, light has a lot of properties. By changing some of these properties, we might very well minimize the impact light pollution has on wildlife."

"Night lighting and anthropogenic sound are not localized to certain habitats and certain countries. It's a global phenomenon," he said. "Clarifying these mechanisms can help develop solutions to biodiversity loss and anthropogenic impacts worldwide."