Culture

Gut's immune response in COVID-19 may not provide efficient protection of other organs

Our guts may not provide long-lasting systemic immunity from COVID-19, which is where immune cells circulate through the body to provide protection to other organs, finds a new study published in Frontiers in Immunology. An analysis of blood samples from patients infected with SARS-CoV-2 revealed that immune cells circulating in the blood, which were triggered by the gut's response to infection, were limited in number when compared to immune cells that had been triggered elsewhere in the body.

"Although the gut is considered an important portal of entry for the virus, the immune response in the blood of COVID-19 patients is dominated by lymphocytes - cells that protect the body from infection - that have been triggered by other areas of the body," says Dr Sebastian Zundler, author of this study and research group leader at the Department of Medicine 1, University Hospital Erlangen, Germany. "Further work is needed, but these findings may have implications for oral COVID-19 vaccines."

Gut response

COVID-19 infection can enter the body via the lungs or the gut, hence the advice for social distancing and frequent handwashing. Zundler's team were keen to understand the role of the gut in providing systemic immunity to this virus.

"My lab is usually interested in immune responses linked to inflammatory bowel disease - an immune-mediated disorder. Since SARS-CoV-2 infection can occur via the intestine, we decided to transfer our knowledge to study this virus," says Zundler.

The team used a technique called flow cytometry to detect and measure the different types of immune cells that were found in the blood samples of patients currently with COVID-19, patients recovered from COVID-19 and those free of the virus.

"There is a special mechanism in the lymphoid tissue of the gut that triggers the production of an imprint marker called "a4b7 integrin". This marker causes T cells to head towards the gut to fight infection. We can use this marker to identify whether there are lymphocytes circulating in the blood that were triggered by the gut's immune response," explains Dr Tanja Müller, lead author of this study, also based at the University Hospital Erlangen.

She continues, "We found relatively few immune cells with this marker in the blood of patients with COVID-19. This could be because of the "dilution" by cells generated at other sites of infection - most probably the lung - or alternatively by the selective attraction of these gut-imprinted immune cells to organs other than the gut, since there was no difference between patients with and without symptoms that suggested an intestinal element to their infection."

Implications for an oral vaccine

The researchers speculate that if the gut-imprinted immune cells are diluted in comparison to immune cells triggered by other parts of the body, there could be implications for the oral-based COVID-19 vaccines currently under development.

"If there are relatively few gut-imprinted immune cells, exposing the intestinal immune system with a SARS-CoV-2 vaccination might not result in substantial circulating immunity and therefore the cross-protection of other organs against the virus," says Müller.

Zundler stresses that further research is needed to understand the significance of their findings.

"Our study adds to our understanding of the human immune response to SARS-CoV-2 infection, but we cannot yet finally answer the question about the fate of the gut-imprinted immune cells - whether they are "diluted" or "attracted" elsewhere. Assessing biopsy samples from the gut and autopsy samples from the lungs will help us to answer this important question."

Credit: 
Frontiers

Understanding spoilage and quality issues may improve American artisan cheesemaking industry

image: Examples of rind defects include (A) unwanted surface molds such as blue mold on Camembert cheese (photograph by B.E. Wolfe), (B) unwanted rind colors, such as purple rind defect (Kamelamela et al., 2018), (C) rind separation from paste in mold ripened cheese (Choi et al., 2016), and (D) unwanted divots or dimples in the rind (photograph by Biango-Daniels).

Image: 
Refer to caption

Philadelphia, April 20, 2021 - American artisan cheese has become increasingly popular over the past few decades. Understanding spoilage concerns and the financial consequences of defects can improve quality, profitability, and sustainability in the American artisan cheesemaking industry. In an article appearing in the Journal of Dairy Science®, scientists from Tufts University took the pulse of artisan cheese producers in the United States through an industry survey.

The authors of this study provide a snapshot of the artisanal cheesemaking community indicating that many (71 percent) are concerned about undesirable surface molds and incorrect or unexpected colors or pigments on rinds (54 percent). Of the 61 cheesemakers surveyed, 18 percent were very concerned about quality and spoilage problems, 39 percent said that their quality standards are not met annually, and 33 percent said their quality standards are not met monthly.

"The growing US cheesemaking industry will require additional resources moving forward that address not only safety but also quality and spoilage concerns," said first author Megan Biango-Daniels, PhD, Biology Department, Tufts University, Medford, MA, USA. "One interesting observation from our data is that cheesemakers, as a group, are unsure about how widespread quality issues are but strongly agree that additional resources to help address quality issues would benefit them personally."

Although 62 percent of survey respondents reported that only between zero and five percent of their product was lost or made less valuable due to quality issues annually, seven percent of cheesemakers had losses of over 20 percent of their product. Nearly all respondents agreed that better quality of their products would lessen waste, boost profits, and enhance production. In answer to open-ended questions, those surveyed said that they would like to have access to additional online resources addressing quality topics and to digital forums to collaborate with experts and peers when problems emerge.

Dr. Biango-Daniels added, "Regardless of what these future resources will look like, it's important that cheesemakers budget for professional development, organizational membership, and continuing education (training online or in-person) in their business plans so that they can afford to invest in the resources that enable production of safe, high-quality cheese."

The study suggests that addressing the concerns of cheesemakers will remain challenging because of resource and tool development barriers, the relatively few scientists who specialize in these subjects, and the limited funding sources available for this type of research.

Credit: 
Elsevier

Flushing a public toilet? Don't linger, because aerosolized droplets do

video: To measure the droplets, researchers used a particle counter placed at various heights of the toilet and urinal to capture the size and number of droplets generated upon flushing.

Image: 
Florida Atlantic University, College of Engineering and Computer Science

Flushing a toilet can generate large quantities of microbe-containing aerosols depending on the design, water pressure or flushing power of the toilet. A variety of pathogens are usually found in stagnant water as well as in urine, feces and vomit. When dispersed widely through aerosolization, these pathogens can cause Ebola, norovirus that results in violent food poisoning, as well as COVID-19 caused by SARS-CoV-2.

Respiratory droplets are the most prominent source of transmission for COVID-19, however, alternative routes may exist given the discovery of small numbers of viable viruses in urine and stool samples. Public restrooms are especially cause for concern for transmitting COVID-19 because they are relatively confined, experience heavy foot traffic and may not have adequate ventilation.

A team of scientists from Florida Atlantic University's College of Engineering and Computer Science once again put physics of fluids to the test to investigate droplets generated from flushing a toilet and a urinal in a public restroom under normal ventilation conditions. To measure the droplets, they used a particle counter placed at various heights of the toilet and urinal to capture the size and number of droplets generated upon flushing.

Results of the study, published in the journal Physics of Fluids, demonstrate how public restrooms could serve as hotbeds for airborne disease transmission, especially if they do not have adequate ventilation or if toilets do not have a lid or cover. Most public restrooms in the United States often are not equipped with toilet seat lids and urinals are not covered.

For the study, researchers obtained data from three different scenarios: toilet flushing; covered toilet flushing and urinal flushing. They examined the data to determine the increase in aerosol concentration, the behavior of droplets of different sizes, how high the droplets rose, and the impact of covering the toilet. Ambient aerosol levels were measured before and after conducting the experiments.

"After about three hours of tests involving more than 100 flushes, we found a substantial increase in the measured aerosol levels in the ambient environment with the total number of droplets generated in each flushing test ranging up to the tens of thousands," said Siddhartha Verma, Ph.D., co-author and an assistant professor in FAU's Department of Ocean and Mechanical Engineering. "Both the toilet and urinal generated large quantities of droplets smaller than 3 micrometers in size, posing a significant transmission risk if they contain infectious microorganisms. Due to their small size, these droplets can remain suspended for a long time."

The droplets were detected at heights of up to 5 feet for 20 seconds or longer after initiating the flush. Researchers detected a smaller number of droplets in the air when the toilet was flushed with a closed lid, although not by much, suggesting that aerosolized droplets escaped through small gaps between the cover and the seat.

"The significant accumulation of flush-generated aerosolized droplets over time suggests that the ventilation system was not effective in removing them from the enclosed space even though there was no perceptible lack of airflow within the restroom," said Masoud Jahandar Lashaki, Ph.D., co-author and an assistant professor in FAU's Department of Civil, Environmental and Geomatics Engineering. "Over the long-term, these aerosols could rise up with updrafts created by the ventilation system or by people moving around in the restroom."

There was a 69.5 percent increase in measured levels for particles sized 0.3 to 0.5 micrometers, a 209 percent increase for particles sized 0.5 to 1 micrometers, and a 50 percent increase for particles sized 1 to 3 micrometers. Apart from the smallest aerosols, comparatively larger aerosols also pose a risk in poorly ventilated areas even though they experience stronger gravitational settling. They often undergo rapid evaporation in the ambient environment and the resulting decreases in size and mass, or the eventual formation of droplet nuclei, can allow microbes to remain suspended for several hours.

"The study suggests that incorporation of adequate ventilation in the design and operation of public spaces would help prevent aerosol accumulation in high occupancy areas such as public restrooms," said Manhar Dhanak, Ph.D., co-author, chair of FAU's Department of Ocean and Mechanical Engineering, and professor and director of SeaTech. "The good news is that it may not always be necessary to overhaul the entire system, since most buildings are designed to certain codes. It might just be a matter of redirecting the airflow based on the restroom's layout."

During the 300-second sampling, the toilet and urinal were flushed manually five different times at the 30-, 90-, 150-, 210-, and 270-second mark, with the flushing handle held down for five consecutive seconds. The restroom was deep cleaned and closed 24 hours prior to conducting the experiments, with the ventilation system operating normally. The temperature and relative humidity within the restroom were 21 degrees Celsius (69.8 degrees Fahrenheit) and 52 percent, respectively.

"Aerosolized droplets play a central role in the transmission of various infectious diseases including COVID-19, and this latest research by our team of scientists provides additional evidence to support the risk of infection transmission in confined and poorly ventilated spaces," said Stella Batalama, Ph.D., dean of the College of Engineering and Computer Science.

Credit: 
Florida Atlantic University

Experimental Biology 2021 press materials available now

Embargoed press materials are now available for the virtual Experimental Biology (EB) 2021 meeting, featuring cutting-edge multidisciplinary research from across the life sciences. EB 2021, to be held April 27-30, is the annual meeting of five scientific societies bringing together thousands of scientists and 25 guest societies in one interdisciplinary community.

Complete a Press Registration Form for complimentary meeting registration and full access to our virtual newsroom. We encourage advance registration as it may take up to a day to receive access.

Join Our Virtual Press Conference

Reporters are invited to join a live Q&A discussion of selected research announcements during a virtual EB press conference held online from 1-1:45 p.m. EDT on Monday, April 26, 2021 (RSVP by Friday, April 23). The press conference will feature the following five research highlights:

Taking Vitamin D Could Lower Heart Disease Risk for People with Dark Skin

Racial disparities in heart disease may be linked to vitamin D deficiency

Could Heart Medications Increase COVID-19 Risk?

Mouse study takes tissue-specific look at how blood pressure medications affect SARS-CoV-2 receptors

How Did Dinosaurs Deliver Bone-Crushing Bites? By Keeping a Stiff Lower Jaw.

New research addresses longstanding mystery on the anatomy of the Tyrannosaurus rex jaw

Cell Study Suggests Pesticide Exposure May Increase COVID-19 Susceptibility

Inflammation-induced mechanism might be linked with higher infection risk for veterans and people with metabolic disorders

Researchers Work to Increase Number of Transplantable Livers

New findings lay groundwork for turning previously unusable donor livers into transplantable organs

Additional Press Materials

Find these materials and more at our virtual newsroom:

New COVID-19 Research

Gene Changes Might Explain Long-Haul COVID-19 Symptoms

Airway cells exposed to SARS-CoV-2 spike protein exhibited persisting changes in gene expression

SARS-CoV-2 Spike Protein Alone May Cause Lung Damage

New mouse model makes it easier and safer to study COVID-19 lung injury

Study Illuminates How COVID-19 Worms Its Way into the Brain

Research helps explain baffling neurological symptoms--and why they're so unpredictable

Five New Insights in the Fight Against COVID-19

Researchers announce new findings on treatments, health impacts and repercussions for science education

Researchers Design Sensor for Fast, Inexpensive On-Site Ebola Detection

Sensor technology requires no special storage; could also be useful for detecting COVID-19

Urine of COVID-19 Patients Could Predict Who Will Develop Severe Disease

Inflammatory markers were higher in people with high blood pressure and diabetes

Our Natural World

Could Corals Use Sound to Communicate?

New evidence suggests corals may have genes involved in receiving or emitting sound

How Does a Nose Evolve into a Blowhole? Study Suggests There's More than One Way

Toothed and baleen whales show different patterns of blowhole development

Brain Development Is Surprisingly Similar between Humans and Other Primates

Study offers first comprehensive view of brain maturation across species

Staying Healthy

'Smart Shirt' Takes a Trip to Space for Science

High-tech shirt non-intrusively monitors astronauts' health during spaceflight

Why Older People Should Chill When It's Hot Out

Cooling off during extreme heat appears to help preserve cellular defenses

Researchers Uncover Potential New Way to Treat Dry Mouth

PDE4 inhibition induces salivation in mice; findings might also have implications for cystic fibrosis

Compound Found in Some Vegetables May Reduce Diabetes-Related Kidney Damage

Phenethyl isothiocyanate, derived from watercress and other cruciferous vegetables, shows benefits in rats

Omega-3 Supplements Help Kids with High Cholesterol Improve Lipid Profile

Fatty acid supplementation could fend off later heart disease in high-risk children

Prolonged Exposure to Extreme Heat and Humidity Increases Risk of Acute Kidney Injury

Findings could help future treatment and prevention measures

Heart Health

Depression Medication Could Also Protect Against Heart Disease

Researchers show antidepression drug also protects against clot formation in human blood

Potential Advancements in Treatment of PTSD and PTSD-related Cardiovascular Disease

Researchers explore renin-angiotensin system gene function for memory processing

Treating Cancer

Capsaicin Analog Could Help Treatment-Resistant Lung Cancer

Small cell lung cancer cells exposed to synthetic analog of chili pepper compound responded better to chemotherapy

Plant Compound Shows Promise Against Triple-Negative Breast Cancer

Cells from women with African American ancestry responded more strongly to the compound

Exercise Science

Got 10 Minutes? That's All You Need for this High-intensity Workout

Four-second cycling sprints improve exercise endurance and power

Dab on Deep Heat Cream to Improve Exercise Performance

Study finds boost in aerobic performance in athletes who used over-the-counter deep heat cream

Environmental Exposures

Five Studies Point to Dangers of Environmental Exposures

New research highlights surprising effects of invisible and often involuntary exposures

Exposure to Roundup® Extends Seizure-like Behavior in Roundworms

Findings have implications for human and environmental health

Other Medical News

Toward a Feasible Alternative to Liver Organ Transplant

New findings could lead to ways to keep transplanted adult liver cells functioning long term

Rapamycin May Exacerbate Age-related Arthritis Despite Life-extending Benefits

Rapamycin impairs mitochondrial function in guinea pig model

Using Big Data to Save Babies

Machine learning could detect lung disorder in preemies better than traditional diagnostics

Light Therapy Helps Veterans Treated for Traumatic Brain Injury

Lightbox improves cognitive function and mood in veterans with TBI, pilot study finds

Self-reported Daytime Sleepiness Is Associated with Telomere Shortening

Shorter telomere length was found in people without sleep apnea

Diabetes Drug Could Protect Against Dangerous Infection

Metformin inhibited C. diff spread in three study models

Contact: media@experimentalbiology.org

EB host societies are the American Association for Anatomy, American Physiological Society, American Society for Biochemistry and Molecular Biology, American Society for Investigative Pathology and American Society for Pharmacology & Experimental Therapeutics.

#expbio | EB on Facebook | EB on Twitter (@expbio)

Credit: 
Experimental Biology

Brain-on-a-chip would need little training

image: Advances in artificial intelligence technology is leading to the development of neural networks that mimic the biology of the brain.

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© 2021 KAUST

A biomimicking "spiking" neural network on a microchip has enabled KAUST researchers to lay the foundation for developing more efficient hardware-based artificial intelligence computing systems.

Artificial intelligence technology is developing rapidly, with an explosion of new applications across advanced automation, data mining and interpretation, healthcare and marketing, to name a few. Such systems are based on a mathematical artificial neural network (ANN) composed of layers of decision-making nodes. Labeled data is first fed into the system to "train" the model to respond a certain way, then the decision-making rules are locked in and the model is put into service on standard computing hardware.

While this method works, it is a clunky approximation of the far more complex, powerful and efficient neural network that actually makes up our brains.

"An ANN is an abstract mathematic model that bears little resemblance to real nervous systems and requires intensive computing power," says Wenzhe Guo, a Ph.D. student in the research team. "A spiking neural network, on the other hand, is constructed and works in the same way as the biological nervous system and can process information in a faster and more energy-efficient way."

Spiking neural networks (SNNs) emulate the structure of the nervous system as a network of synapses that transmit information via ion channels in the form of action potential, or spikes, as they occur. This event-driven behavior, implemented mathematically as a "leaky integrate-and-fire model," makes SNNs very energy efficient. Plus, the structure of interconnected nodes provides a high degree of parallelization, which further boosts processing power and efficiency. It also lends itself to implementation directly in computing hardware as a neuromorphic chip.

"We used a standard low-cost FPGA microchip and implemented a spike-timing-dependent plasticity model, which is a biological learning rule discovered in our brain," says Guo.

Importantly, this biological model does not need teaching signals or labels, allowing the neuromorphic computing system to learn real-world data patterns without training.

"Since SNN models are very complex, our main challenge was to tailor the neural network settings for optimal performance," says Guo. "We then designed the optimal hardware architecture considering a balance of cost, speed and energy consumption."

The team's brain-on-a-chip proved to be more than 20 times faster and 200 times more energy efficient than other neural network platforms.

"Our ultimate goal is to build a compact, fast and low-energy brain-like hardware computing system. The next step is to improve the design and optimize product packaging, miniaturize the chip and customize it for various industrial applications through collaboration," Guo says.

Credit: 
King Abdullah University of Science & Technology (KAUST)

Atomic-level insights gained for a key lipid-binding protein implicated in cancer

image: Dr. Marassi is director and professor in the Cell and Molecular Biology of Cancer Program at Sanford Burnham Prebys.

Image: 
Sanford Burnham Prebys

LA JOLLA, CALIF. - April 20, 2021 Scientists at Sanford Burnham Prebys have identified, at an atomic level, how a part of a protein called PLEKHA7 interacts with a cell's membrane to regulate important intercellular communications. The research, published in the journal Structure, points to hotspots within PLEKHA7 as targets for drugs. These targets could be key in designing treatments for advanced colon, breast and ovarian cancers.

The region, or domain, in PLEKHA7 that the researchers examined, pleckstrin homology (PH), is commonly found in proteins that regulate the movement of cells as well as other important cellular activities. If the interaction between the PH domain and the lipids that comprise cell membranes is disrupted, diseases such as cancer can occur.

"PH domains have been studied for some time but examining their interactions with membrane-associated lipids has been challenging," says Francesca M. Marassi, Ph.D., professor and director of the Cell and Molecular Biology of Cancer Program at Sanford Burnham Prebys and corresponding author of the study. "We optimized our structural investigations by using an artificial membrane disc several nanometers in size. This nanodisc is a 'substitute' cell membrane and has been an important tool in overcoming obstacles in studying structural aspects of fatty interfaces, such as those involving lipids."

The investigators used several techniques to detail the precise areas where the PH domain interacted with lipids in a cell's membrane. Each of the three techniques was equally important: X-ray crystallography provided a snapshot of the structure; magnetic resonance showed the precise association of the PH domain with the lipid membrane surface; and computer simulations put all of this information together to generate a dynamic movie of the interaction.

"We were able to determine that the PH domain interacts with the cellular membrane at several locations simultaneously, thereby demonstrating the key role of the membrane as a platform for directing cell signaling and adhesion," says Marassi. "We found at least three sites along the PH domain that are engaged in binding lipids. Having multiple sites is crucial, because if you think of the PH binding sites as a zipper between proteins and lipids, each additional notch engaged by a zipper makes the binding stronger and more resistant to being pulled apart."

One of the reasons the scientists were interested in exploring PLEKHA7 was that the protein has recently been identified as a potential anti-cancer target. However, its molecular mechanism of action has been uncertain. Additionally, the researchers were interested in the PH domain because it has been implicated in advanced breast, renal and ovarian cancers and, most prominently, plays an important role in colorectal cancer.

"Clinicians have shown that PLEKHA7 is elevated in patients with colorectal cancer, and its levels increase as the disease worsens. It has also been shown that inhibiting PLEKHA7 decreases cellular proliferation and migration," says Marassi. "Therefore, the PLEKHA7 PH domain might be a useful drug target, but more work is needed to develop agents with greater potency and optimized pharmacological properties."

As a next step, the scientists hope to share their structural images with colleagues in other labs at Sanford Burnham Prebys, and elsewhere, to screen for drugs that target the PH domain and lipid membrane binding sites.

Credit: 
Sanford Burnham Prebys

Little Foot fossil shows early human ancestor clung closely to trees

video: The USC-led research team used advanced CT scans and comparisons with humans, primates and other fossils to interpret Little Foot's shoulder bones, seen in this video animation.

Image: 
Kristian Carlson

A long-awaited, high-tech analysis of the upper body of famed fossil "Little Foot" opens a window to a pivotal period when human ancestors diverged from apes, new USC research shows.

Little Foot's shoulder assembly proved key to interpreting an early branch of the human evolutionary tree. Scientists at the Keck School of Medicine of USC focused on its so-called pectoral girdle, which includes collarbones, shoulder blades and joints.

Although other parts of Little Foot, especially its legs, show humanlike traits for upright walking, the shoulder components are clearly apelike, supporting arms surprisingly well suited for suspending from branches or shimmying up and down trees rather than throwing a projectile or dangling astride the torso like humans.

The Little Foot fossil provides the best evidence yet of how human ancestors used their arms more than 3 million years ago, said Kristian J. Carlson, lead author of the study and associate professor of clinical integrative anatomical sciences at the Keck School of Medicine.

"Little Foot is the Rosetta stone for early human ancestors," he said. "When we compare the shoulder assembly with living humans and apes, it shows that Little Foot's shoulder was probably a good model of the shoulder of the common ancestor of humans and other African apes like chimpanzees and gorillas."

The apelike characteristics will likely attract considerable intrigue as science teams around the world have been examining different parts of the skeleton to find clues to human origins. The USC-led study, which also involved researchers at the University of Wisconsin, the University of Liverpool and the University of the Witwatersrand in South Africa, among others, was published today in the Journal of Human Evolution.

The journal devoted a special issue to Little Foot analyses from a global research group, which looked at other parts of the creature's skeleton. The process is somewhat akin to the story of blind men and the elephant, each examining one part in coordination with others to explain the whole of something that's not fully understood.

The Little Foot fossil is a rare specimen because it's a near-complete skeleton of an Australopithecus individual much older than most other human ancestors. The creature, probably an old female, stood about 4 feet tall with long legs suitable for bipedal motion when it lived some 3.67 million years ago. Called "Little Foot" because the first bones recovered consisted of a few small foot bones, the remains were discovered in a cave in South Africa in the 1990s. Researchers have spent years excavating it from its rock encasement and subjecting it to high-tech analysis.

While not as widely known as the Lucy skeleton, another Australopithecus individual unearthed in East Africa in the 1970s, Carlson said Little Foot is older and more complete.

The USC-led research team zeroed in on the shoulder assemblies because Little Foot provides the oldest and most intact example of this anatomy ever found. Those bones provide telltale clues of how an animal moves. In human evolution, he said, these parts had to change form before our ancestors could live life free of trees, walk the open savannah and use their arms for functions other than supporting the weight of the individual.

The scientists compared the creature's shoulder parts to apes, hominins and humans. Little Foot was a creature adapted to living in trees because the pectoral girdle suggests a creature that climbed trees, hung below branches and used its hands overhead to support its weight.

For example, the scapula, or shoulder blade, has a big, high ridge to attach heavy muscles similar to gorillas and chimpanzees. The shoulder joint, where the humerus connects, sits at an oblique angle, useful for stabilizing the body and lessening tensile loads on shoulder ligaments when an ape hangs beneath branches. The shoulder also has a sturdy, apelike reinforcing structure, the ventral bar. And the collarbone has a distinctive S-shaped curve commonly found in apes.

Those conclusions mean that the structural similarities in the shoulder between humans and African apes are much more recent, and persisted much longer, than has been proposed, Carlson said.

"We see incontrovertible evidence in Little Foot that the arm of our ancestors at 3.67 million years ago was still being used to bear substantial weight during arboreal movements in trees for climbing or hanging beneath branches," he said. "In fact, based on comparisons with living humans and apes, we propose that the shoulder morphology and function of Little Foot is a good model for that of the common ancestor of humans and chimpanzees 7 million to 8 million years ago."

The scientists were able to achieve remarkably clear images of the fossils. That's because the bones, painstakingly excavated for many years, are in good condition and uniquely complete. The scientists examined them using micro-CT scans, which can detect minute features on the surface of an object, peer deep inside a bone, measure the density of an object and generate a 3D model without harming the fossil.

Credit: 
University of Southern California

Cool and COVID-safe: How radiant cooling could keep our cities comfortable and healthy

image: The researchers demonstrated their cooling system by building a pavilion in Singapore featuring a system of chilled tubes enclosed within a condensation-preventing membrane.

Image: 
Lea Ruefenacht

A novel system of chilled panels that can replace air conditioning can also help reduce the risk of indoor disease transmission, suggests new analysis from the University of British Columbia, University of Pennsylvania and Princeton University.

The researchers computed air conditioning requirements in 60 of the world's most populous cities--with the additional ventilation required due to COVID-19. Then, they compared the energy costs with their cooling method, using the chilled panels and natural ventilation.

The results, published in the COVID-19 edition of Applied Energy, showed that the alternative solution can save up to 45 per cent of the required energy, while ensuring building occupants are comfortable and rooms are adequately refreshed.

Dr. Adam Rysanek, a professor in the school of architecture and landscape architecture at UBC and co-author of the paper, notes that many public health guidelines, as well as building industry bodies, recommend increasing the flow of fresh, outdoor air into buildings in order to reduce the risk of spreading COVID-19 and other diseases.

"However, if we continue to rely on conventional HVAC systems to increase indoor fresh air rates, we may actually double energy consumption. That's the nature of conventional HVAC."

"Alternatively, we can encourage people to install new types of radiant cooling systems, which allow them to keep their windows open even when it's hot outside. These alternative systems can provide a sufficient level of thermal comfort, increase protection against disease while lessening the impact on the environment," noted Rysanek, director of the Building Decisions Research Group at UBC's faculty of applied science.

Rysanek and his colleagues earlier demonstrated their cooling system in the hot and humid climate of Singapore. They built a public pavilion featuring a system of chilled tubes enclosed within a condensation-preventing membrane. This allowed occupants to feel comfortable, and even cold, without changing the air temperature surrounding the human body.

"You can think of it as lean A/C--or, even better, as a green alternative to energy-guzzling air conditioning," said Rysanek.

Toronto is one of the cities included in the latest analysis, as are Beijing, Miami, Mumbai, New York and Paris. In all these regions, peak summer temperatures can soar past 35 degrees Celsius (95 degrees Fahrenheit).

"A key impact of climate change is the accelerating rise in average and peak temperatures, particularly in urban areas. We are expecting the appetite for indoor cooling will ramp up in the years ahead. Yet, if we want to mitigate urban heat and ensure people are healthy and comfortable while reducing our energy use, we need to seriously consider revolutionising our historical approach to air-conditioning," adds Rysanek.

Rysanek notes that, though chilled panel systems have been around for decades, adding the special membrane devised by the research team could be the key to making it a commercially viable alternative to traditional HVAC systems in all climates.

Interview languages: English

Credit: 
University of British Columbia

Reliably detecting cocoa off-flavors

image: Photo of a cocoa bean, You can see the shell and in the part where the shell was removed, the embryo.

Image: 
Martin Steinhaus

Musty, moldy, smoky or horse dung-like smelling cocoa is not suitable for chocolate production. As part of a larger research project, a team of scientists led by Martin Steinhaus from the Leibniz Institute for Food Systems Biology at the Technical University of Munich has identified the odorants responsible for such off-flavors. The food industry can now use these results to objectively assess the sensory quality of fermented cocoa based on odorant concentrations. The research team published the data in the Journal of Agricultural and Food Chemistry.

Who likes chocolate that smells like smoke or mold, or chocolate whose aroma is reminiscent of a horse stable or of mothballs? Off-flavors are a major problem, especially for small and medium-sized enterprises. However, also for larger companies, off-flavor-tainted cocoa batches can cause immense economic damage, posing the need for their reliable identification during the incoming goods inspection. Until now, this has only been possible with some limitations by using a trained sensory panel, since no approach to objectively evaluate off-flavors in cocoa on the basis of the concentrations of the causative odorants was available.

As part of a project of the Research Association of the German Food Industry, the team led by food chemist Martin Steinhaus has now made a significant contribution to solving this problem. Using the molecular sensory science concept established at the Leibniz Institute, the research group has identified the key odorants that chiefly contribute to typical off-flavors in fermented cocoa.

Off-flavors from hammy-smoky to moldy-musty

In cocoa samples with hammy-smoky off-flavors, the team identified six crucial odorants. The substances smelled smoky, hammy, phenolic or horse stable-like. In samples with a moldy-musty odor, the researchers found additional four off-flavor compounds. These smelled moldy, musty, beetroot-like, fecal- or mothball-like. The research team determined the odor threshold values of the identified substances in order to derive maximum concentration limits.

In its latest publication, for example, the team recommends a maximum tolerable concentration for the off-flavor substance geosmin of 1.6 micrograms per kilogram of fermented cocoa. Even in the lowest concentrations, this odorant has a musty, earthy smell reminiscent of beetroot. Geosmin is presumably of bacterial origin. For fecal, mothball-like smelling 3-methyl-1H-indole, the researchers recommend a limit of 1.1 micrograms per kilogram of fermented cocoa.

Odorant distribution is also important

The research team's findings also show that about 40 to 65 percent of total geosmin is found in the seed coat (testa) of fermented cocoa beans. In contrast, the off-flavor substance 3-methyl-1H-indole was predominantly found inside the beans. "The uneven distribution of the two odorants between the seed coat and the embryo is another important aspect that chocolate manufacturers should consider when testing fermented cocoa," says Martin Steinhaus. "At the moment, we do not know how much geosmin is transferred from the shells into the embryo during the roasting process. Therefore, it might be reasonable to remove the seed coats before roasting rather than after roasting."

Credit: 
Leibniz-Institut für Lebensmittel-Systembiologie an der TU München

Differing immune responses discovered in asymptomatic cases vs those with severe COVID-19

The largest study of its type in the UK has identified differences in the immune response to COVID-19, between people with no symptoms, compared to those suffering a more serious reaction to the virus.

Researchers from the Wellcome Sanger Institute, Newcastle University, University College London, University of Cambridge, EMBL's European Bioinformatics Institute (EMBL-EBI) and their collaborators within the Human Cell Atlas initiative, found raised levels of specific immune cells in asymptomatic people. They also showed people with more serious symptoms had lost these protective cell types, but gained inflammatory cells. These differences in the immune response could help explain serious lung inflammation and blood clotting symptoms, and could be used to identify potential targets for developing therapies.

The research, published today (20th April 2021) in Nature Medicine, is one of the only studies to include people who were asymptomatic. This large-scale collaborative study is part of the Human Cell Atlas* initiative to map every cell type in the human body, to transform our understanding of health, infection and disease.

So far, the COVID-19 global pandemic has caused millions of deaths and many more infections worldwide. Symptoms vary widely in severity and can range from a mild cough to severe respiratory distress, blood clots and organ failure. Several previous studies have highlighted a complex immune response in the blood, but until now the full coordinated immune response and how this differs between symptomatic and asymptotic patients had not been investigated in detail.

In a new study to understand how different immune cells responded to the infection, a large team of researchers came together to analyse blood from 130 people with COVID-19. These patients came from three different UK centres (Newcastle, Cambridge and London) and ranged from asymptomatic to critically severe.

The team performed single-cell sequencing from ~800,000 individual immune cells, along with detailed analysis of cell surface proteins and antigen receptors found on immune cells in the blood. They revealed differences in multiple types of immune cells that are involved in the body's response to COVID-19.

In those with no symptoms, the team found increased levels of B cells that produce antibodies that are found in mucus passages, such as the nose. These antibodies may be one of our first line of defence in COVID-19. However, these protective B cells were missing in people with serious symptoms, indicating the importance of an effective antibody-associated immune response at the nose and other mucus passages.

The team discovered that whereas patients with mild to moderate symptoms, had high levels of B cells and helper T-cells, which help fight infection, those with serious symptoms had lost many of these immune cells, suggesting that this part of the immune system had failed in people with severe disease.

In contrast, people with more serious symptoms leading to hospitalisation had an uncontrolled increase in monocytes and killer T-cells, high levels of which can lead to lung inflammation. Those with severe disease also had raised levels of platelet-producing cells, which help blood to clot.

Professor Muzlifah Haniffa, senior author from Newcastle University and Senior Clinical Fellow at the Wellcome Sanger Institute, said: "This is one of the only studies of its kind that looks at samples collected from asymptomatic people, which helps us start to understand why some people react differently to COVID-19 infection. It could also explain symptoms such as lung inflammation and blood clots. The immune system is made up of lots of different groups of cells, similar to the way an orchestra is made up of different groups of instruments, and in order to understand the coordinated immune response, you have to look at these immune cells together."

While it is not yet understood how the infection stimulates these immune responses, the study gives a molecular explanation for how COVID-19 could cause an increased risk of blood clotting and inflammation in the lungs, which can lead to the patient needing a ventilator. This also uncovers potential new therapeutic targets to help protect patients against inflammation and severe disease. For example, it may be possible to develop treatments that decrease platelet production or reduce the number of killer T-cells produced, however more research is required.

Professor Menna Clatworthy, senior author and Professor of Translational Immunology at the University of Cambridge and Wellcome Sanger Institute Associate Faculty, said: "This is one of the most detailed studies of immune responses in COVID-19 to date, and begins to help us understand why some people get really sick while others fight off the virus without even knowing they have it. This new knowledge will help identify specific targets for therapy for patients that get sick with COVID-19."

In the future, research may identify those who are more likely to experience moderate to severe disease by looking at levels of these immune cells in their blood.

This study used samples from three centres in the UK, and found that some antibody responses were similar in individuals in one geographic area compared with those at a different centre, hinting that this part of the immune response may be tailored to different variants of the virus.

Dr John Marioni, senior author and Head of Research at EMBL's European Bioinformatics Institute (EMBL-EBI) and Senior Group Leader at the Cancer Research UK Cambridge Institute, said: "Using data from three different centres has allowed us to look at how people react to COVID-19 throughout the UK. The amount of data collected in this study has given us crucial insight into the immune reaction in various different severities of COVID-19 infection."

Professor Berthold Göttgens, senior author and Professor of Molecular Haematology at the University of Cambridge, said: "Along with the findings, the way this study was conducted is noteworthy, as it was a new way of doing biomedical science. By bringing different experts together, we were able to employ a divide and conquer approach, which allowed us to complete the work in extra quick time. This study required a large teamwork effort, in the middle of the pandemic when labs were being shut down. This was an incredibly rewarding study to work on, with everyone understanding the importance of the work and willing to go the extra mile."

Dr Sarah Teichmann, senior author from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: "This is a great example of using the Human Cell Atlas to understand COVID-19 and identify which of our cells are critical for infection and treatment. This information can be used to better understand why different people react to coronavirus in different ways. The data is openly accessible and can provide a basis for developing potential new therapies, to reduce the spread of the virus, or to protect those who start to develop severe disease."

Credit: 
Wellcome Trust Sanger Institute

Review summarizes known links between endocrine disruptors and breast cancer risk

Exposure to certain endocrine-disrupting chemicals could elevate the risk of breast cancer, according to a new comprehensive systematic review of epidemiological research. However, for many chemicals, evidence is inconsistent or still limited. The review was carried out by researchers at the universities of Hong Kong and Eastern Finland and published in Critical Reviews in Food Science and Nutrition.

Endocrine-disrupting chemicals (EDCs) can interfere with the body's hormonal system, also called the endocrine system, and are widely present in the environment. They originate from a variety of sources, including pesticides, plasticisers and other industrial and pharmaceutical chemicals, as well as natural sources. Humans are often exposed to EDCs through food, but other possible exposure routes include drinking water, skin contact and air.

Breast cancer accounts for the majority of women's cancers. There has been an increasing interest in the role of estrogene-mimicking EDCs, so called xenoestrogens, in the development of breast cancer. They comprise a broad range of pesticides, synthetic chemicals, phytoestrogens and certain mycotoxins. The researchers reviewed 131 epidemiological studies evaluating the link between xenoestrogen exposure and breast cancer. Most studies assessed exposures by measuring the EDCs and their metabolites in urine, serum, plasma or adipose tissues.

Some may be genetically more vulnerable to EDCs

According to the review, the nowadays widely banned pesticide DDT is one of the most studied EDCs in relation to breast cancer risk. Out of 43 epidemiological studies, eleven reported positive associations between DDT or its metabolites in lipid, serum or plasma and breast cancer incidence. Nine reported higher DDT levels among women with breast cancer than among controls. In a few studies, DDT was linked to estrogen-positive breast cancer or the association to breast cancer risk depended on genotype.

Polychlorinated biphenyls, PCBs, are a large group of compounds earlier much used in electrical devices, surface coatings and other purposes. The review of 50 studies found the association between total PCBs and breast cancer risk to be inconsistent. However, 19 studies linked certain PCBs to a higher breast cancer incidence. Similar to DTT, PCBs accumulate in the adipose tissue and in the food chain and can be excreted in breast milk.

Perfluorooctanoid acid (PFOA) found in some food packaging and cookware was linked to breast cancer risk in three out of five epidemiological studies. Some studies found an association between cancer risk and certain genotypes both for PCBs and PFOAs.

DDT, PCBs ja PFOA are POP substances, persistent organic pollutants, the use of which is strictly regulated. DDT ja PCBs are old POP substances and their levels in the environment are decreasing. PFOA is a newer POP substance.

Phytoestrogens were found beneficial in some, but not all studies

Phytoestrogens are natural plant estrogens that have been suggested to prevent breast cancer. Genistein is a phytoestrogen found in soy products. The review included 29 epidemiological studies focusing on genistein, 18 of which linked it to a lower breast cancer risk, although some only in certain age groups or populations.

For most EDCs included in the review, the link to breast cancer has been investigated in only a few epidemiological studies. Phtalates and bisphenol A (BPA), for example, are used in plastic packaging and can transfer to food. According to the review, four out of six studies linked phthalates to increased breast cancer risk. BPA was linked to more aggressive tumours in one study, but two other epidemiological studies found no link to breast cancer.

Parabens are common preservatives in foods and cosmetic products and considered possible endocrine disruptors. The only epidemiological study on the topic reported a link between paraben exposures, breast cancer risk and mortality following breast cancer.

Oral contraceptive use was linked to an increased breast cancer risk in seven out of eight epidemiological studies, but there were controversies on how duration or discontinuation of oral contraceptive use affected the risk.

The review also included the herbicide atrazine, the industrial by-product dioxine, mycotoxins produced by food and crop molds, and PBDEs found in household furniture coatings and appliances, but epidemiological studies on their links to breast cancer risk were still scarce and often inconsistent.

The writers point out that for EDCs to disrupt endocrine functions, dose, time, duration and age at exposure all matter. In addition, as multiple EDCs coexist in the environment, more research is needed to evaluate their interactive effects on breast cancer risk.

The review also suggests that genotypes could determine whether EDC exposure affects breast cancer risk, and more research is needed on this topic. "One example is the polymorphism of the CYP1A1 gene, which is responsible for estrogen metabolism."

According to the writers, next-generation technologies, such as genome sequencing, proteomics or epigenomics, can help identify new exposure biomarkers with better sensitivity and specificity. "These technologies will also pave way to better assessment of past exposure and prediction of future risks, by taking into account an individual's genetic profile."

Credit: 
University of Eastern Finland

"Molecular Tomographer" algorithm maps gene expression in space

As we accumulate more and more gene-sequencing information, cell-type databases are growing in both size and complexity. There is a need to understand where different types of cells are located in the body, and to map their gene expression patterns into specific locations in tissues and organs. For example, a gene can be actively expressed in one cell while suppressed in another.

One way of mapping genes into tissues is a technique called in situ hybridization. Simply put, a target gene is tagged ("hybridized") with a fluorescent marker within the sections of the tissue it is located in (the "in situ" part). The sections are then visualized under a specialized microscope to see where the gene "lights up". Consecutive photographs of each section are then put together to generate a "spatial" map of the gene's location inside the tissue.

The problem with methods that use in situ hybridization is that, as the number of target genes grows, they start to become complicated, require specialized equipment, and force scientists to select their targets beforehand, a process that can be laborious if the goal is to reconstruct a full map of gene distribution across tissues.

"Spatializing" sequencing data

Now, scientists at EPFL's School of Life Sciences have created a computational algorithm called Tomographer, which can transform gene-sequencing data into spatially resolved data such as images, and does so without needing a microscope. The work was carried out by the research group of Gioele La Manno, and is now published in Nature Biotechnology.

In the new Tomographer technique, the tissue is first cut along the axis of interest into consecutive sections, each of which is then sliced into tissue strips at different angles. Cells from the strips are then broken down to collect their total messenger RNA (mRNA). Each mRNA corresponds to a gene that was active in the cell. The measurements resulting from the strips can be then used as input to the Tomographer algorithm to reconstruct spatial gene-expression patterns across the tissue.

"The Tomographer algorithm opens a promising and robust path to "spatialize" different genomics measurement techniques," says Gioele La Manno. As an application, the scientists used Tomographer to spatially map the molecular anatomy of the brain of the Australian Bearded Dragon (Pogona vitticeps) - a non-model organism, demonstrating how versatile the algorithm can be.

"Ever since I started med school, I have been admiring the way computer tomography revolutionized the way we examine organs and body parts," says Christian Gabriel Schneider, one of the study's lead authors. "Today, I am very proud to be part of a team that has developed a molecular tomography technology. So far, we have focused on applications in neurodevelopmental biology, but in the future, we can certainly imagine molecular tomography becoming a constituent in personalized medicine."

"It was an exciting opportunity to develop an accessible and flexible computational method that has the potential to facilitate progress in the health sciences," adds Halima Hannah Schede, the study's other lead author. "I am very much looking forward to seeing what other spatially resolved biological data forms will be brought to light with Tomographer."

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Scientists at IRB Barcelona discover the cause of neurodegeneration in Lafora disease

image: Bodies that accumulate in the disease disappear when the ability of astrocytes to produce glycogen is removed.

Image: 
IRB Barcelona

Lafora disease is an inherited neurodegenerative condition that initially develops with seizures in adolescence and evolves with progressive degeneration of the nervous system to death, about ten years after its onset. It is characterised by the accumulation of abnormal glycogen aggregates called Lafora bodies in the brain. There is currently no treatment for this condition, although some therapies are being tested in clinical trials.

Led by Dr. Joan Guinovart, emeritus professor of the University of Barcelona (UB) and also group leader of CIBERDEM, the Metabolic Engineering lab at IRB Barcelona has discovered that Lafora bodies that accumulate in glial cells, which are essential for the proper functioning of the nervous system, are responsible for the neurodegeneration associated with the disease.

For this study, Dr. Guinovart's group generated a mouse model of Lafora disease, in which they prevented glycogen from accumulating in glial cells. They found that these mice did not develop neurodegeneration.

"For years, it was believed that the disease was caused by the accumulation of Lafora bodies only in neurons, but now we have shown that neurodegeneration is caused by accumulations in glial cells," says Dr. Jordi Duran, co-director of the study.

"This discovery has important implications for the design of treatments for the disease and we now intend to investigate the mechanism by which glycogen deposits cause this damage. We will also study the possible role of this pathological mechanism in other neurodegenerative diseases," explains Dr. Duran.

The study also involved the laboratories led by Dr. José Antonio del Río, full professor of the UB (at the Institute for Bioengineering of Catalonia and the UB's Institute of Neurosciences) and Professor Matthew Gentry (at the University of Kentucky)..

A consortium supported by the association of affected families

This project has been developed within the framework of a global consortium for the study of Lafora disease, coordinated by the University of Kentucky in the US. In 2016, the consortium received $7.7 M from NIH (U.S. National Institutes of Health) for a period of five years. The consortium was promoted by Chelsea's Hope, an association of families in the US affected by Lafora disease, which in 2014 brought together leading specialists to foster research into the disease.

Credit: 
Institute for Research in Biomedicine (IRB Barcelona)

Database developed on key mollusk to study pollution in coastal areas

image: Members of the team that conducted the new research.

Image: 
University of Córdoba

Scrobiculariaplana is a type of wedge clam widely found along the coasts and estuariesof northern Europe, the Mediterranean and West Africa. Like other mollusks, it is used as a bioindicator to study pollution in these types of ecosystems, for its ability to accumulate heavy metals and organic pollutants.

A new study has managed to identify the transcriptome and the associated proteome of this bivalve, a finding that could represent an important leap forward in the early detection of pollutants in coastal areas. While the genome is the DNA content comprising the genetic information essential for life, the transcriptome includes only the information on genes that are expressed, while the proteome is the totality of proteins expressed at a given time and under specific conditions. Therefore, its reconstruction is key to understanding the molecular effects of pollution.

Thanks to this finding, the study has managed to identify proteins associated with a total of 174 biological processes. Among these are various molecular functions related to stress response mechanisms suffered by these organisms when they are subjected to pollution and its effects.

The work began with collaboration with the Institute of Marine Sciences of Andalusia, the "Molecular Biology of Stress Response Mechanisms" at the University of Cordoba, and the Central Research Support Service (SCAI) of the university institution, which saw to the bio-informatics component, key to the reconstruction of the transcriptome.

After isolating RNA samples from this mollusk under controlled conditions, explained researcher Carmen Michán, small genetic sequences were extracted. The study managed to combine three mathematical algorithms to order all these small fragments, reconstruct entire genes, and bring together all the pieces of this great biological puzzle.

This software tool provides a solid database for biomolecular analysis ,and constitutes a beacon to guide future work. Furthermore, according to Professor José Alhama, another of the researchers who participated in the study, "having this tool increases the likelihood of success of new studies, not only in studies with this specific bivalve, but also in other similar mollusks." The researcher explained that no similar study had been carried out on organisms of this type. Now, this reference map could help better gauge the effects of pollution on marine ecosystems before the damage is irreparable.

Credit: 
University of Córdoba

URI oceanographers reveal links between migrating Gulf Stream and warming ocean waters

image: An animated map and time series (same color convention) of the 2008 temperature anomaly on the Northwest Atlantic Shelf, highlighting the rapid warming in the most recent decade.

Image: 
(Animation by Afonso Gonçalves Neto)

KINGSTON, R.I., -- April 20, 2021 -- The Northwest Atlantic Shelf is one of the fastest-changing regions in the global ocean, and is currently experiencing marine heat waves, altered fisheries and a surge in sea level rise along the North American east coast. A new paper, "Changes in the Gulf Stream preceded rapid warming of the Northwest Atlantic Shelf," published in Communications Earth & Environment by recent URI Graduate School of Oceanography graduate Afonso Gonçalves Neto reveals the causes, potential predictability and historical context for these types of rapid changes.

"We used satellite data to show that when the Gulf Stream migrates closer to the underwater plateau known as the Grand Banks of Newfoundland, as it did after 2008, it blocks the southwestward transport of the Labrador Current that would otherwise provide cold, fresh, oxygen-rich water to the North American shelf," said lead author Gonçalves Neto. This mechanism explains why the most recent decade has been the hottest on record at the edge of the Northeast United States and Canada, as the delivery system of cold water to the region got choked off by the presence of the Gulf Stream.

The URI research team noted the importance of finding that the satellite-observed signature of the Gulf Stream's position relative to the Grand Banks precedes subsurface shelf warming by over a year. "By monitoring satellite observations for changes near the Grand Banks, we can predict changes coming to the Northeast U.S. shelf with potentially enough lead time to inform fishery management decision-making," said GSO graduate student and co-author Joe Langan.

The Grand Banks of Newfoundland is hardly a stranger to attention. It was near this feature that an iceberg sank the R.M.S. Titanic, one impetus for creation of the International Ice Patrol. The Ice Patrol has been collecting oceanographic data in this region for over a century, allowing the URI team to put recent satellite observations in a much longer-term context. Though the 2008 shift at the edge of the Grand Banks created warmer and saltier conditions than ever recorded since 1930, there was a similar shift in the 1970s relative to the decades preceding it. Thus, the circulation change directly observed by satellites might have had a precedent about 50 years ago.

Jaime Palter, GSO associate professor of oceanography and co-author of the study, marveled at the long record, and what remains unknown. "We still don't know what caused the abrupt shift of the circulation near the Grand Banks inferred in the 1970s and observed in 2008, or whether this is the new normal for the circulation and the temperatures of the northeast shelf," said Palter. "There are modeling studies that suggest that a slowdown of the Atlantic Meridional Overturning Circulation can cause the types of changes we observed, but the connection remains to be made in the observational record."

Credit: 
University of Rhode Island