Culture

The field of structural biology has made enormous strides, peering into the activities of nature at the tiniest scale. Such investigations are critical for charting the behavior of important macromolecules and understanding their essential role in living organisms.

Researchers at the Biodesign Center for Applied Structural Discovery and ASU's School of Molecular Sciences have taken a new approach to studying molecules of life, examining not only their static structures at high resolution but the all-important dynamic movements of such molecules as they carry out biological functions.

The new method involves an aggressive reprocessing of data obtained through a groundbreaking technique known as cryogenic electron microscopy or cryo-EM. Here, molecules targeted for study are flash-frozen in a thin membrane of ice before being subjected to electron microscopy. Tens or even hundreds of thousands of still images are collected, then reassembled by means of computer.

The technique offers a powerful alternative to X-ray crystallography for probing the molecular world in keen detail. Indeed, cryo-EM excels in the areas of study that are most challenging for X-ray crystallography, the imaging of large protein complexes resistant to conventional crystallization methods.

Although early iterations of cryo-EM struggled to compete with the extreme image resolution characteristic of X-ray crystallography, rapid advances in the field now enable cryo-EM to produce stunning macromolecular images at near-atomic-resolution.

In the new study, Abhishek Singharoy and his colleagues demonstrate that cryo-EM can be pushed to even greater extremes of clarity, by extracting precious information previously buried in the reams of cryo-EM data.

"Now, we can actually see minimum free-energy pathways image-by-image during a simulation," Singharoy says. "It was impossible to see energetically feasible molecular movies before. Now cryo-EM, machine learning and molecular dynamics simulations have got us there."

Abhishek is joined by joint first authors Ali Dashti and Ghoncheh Mashayekhi of the Department of Physics, University of Wisconsin Milwaukee and ASU researcher Mrinal Shekhar. The new study is the result of a collaboration between five groups: Abbas Ourmazd's, and Peter Schwander's at the University of Wisconsin in Milwaukee, Joachim Frank's at Columbia Medical Center, Amedee des Georges at CUNY, and Singharoy at ASU.

The findings are reported in the current issue of the journal Nature Communications.

Applying the new strategy pioneered by co-authors Abbas Ourmazd and 2017 Chemistry Nobel Laureate Joachim Frank, which involves mathematical techniques of geometric machine learning combined with classical molecular dynamics simulations, helped researchers capture the fleeting movements of ryanodine receptor type 1, an important calcium channel able to bind other molecules. Subtle conformational changes of the receptor play a crucial role in the contraction of skeletal muscle and muscles of the heart, once the receptor has been triggered by a specific binding molecule.

Using single-particle cryo-EM, the group was able to assemble impressive molecular movies of ryanodine receptor type 1's continuous conformational changes, built from some 800,000 cryo-EM snapshots of molecules trapped in ice, like insects entombed in amber.

Combining snapshots that were intermediary between the fully closed and open conformations helped capture this receptor's structural shape-shifting before and after binding by activating molecules.

The new technique will be a boon in practical areas, particularly, drug discovery, while helping to resolve foundational issues in molecular biology.

New research by an international team of chemists describes a new type of artificial cell that can communicate with other cells within the body--with potential applications in the field of smart pharmaceuticals.

"In the future, artificial cells like this one could be engineered to synthesizes and deliver specific therapeutic molecules tailored to distinct physiological conditions or illnesses--all while inside the body," explained Sheref Mansy, professor in the University of Alberta's Department of Chemistry, who co-authored this study in collaboration with researchers at the University of Trento, Italy.

The artificial cells work by detecting changes in their environment within the body. In response, the artificial cell creates and releases a protein signal that influences the behaviour of other cells within the body. "In this way, the changing needs of the host would be rapidly met in a manner that does not flood the entire organism with drug molecules," said Mansy.

Mansy's lab is the first to build artificial cells that can chemically communicate with and influence the behaviour of natural living cells--first with bacteria, and now with cells found in multicellular organisms. "This work begins to bridge the divide between more theoretical 'what is cellular life' type of work and applicative, useful technologies," added Mansy.

Researchers from the OU Institute for Environmental Genomics and Department of Microbiology and Plant Biology lead a study that aims to better understand ecological community assembly mechanisms in response to climate warming.

"Understanding community assembly rules is a longstanding issue of ecologists," said Jizhong Zhou, the director of the Institute for Environmental Genomics and a George Lynn Cross Research Professor in the OU College of Arts and Sciences. "We developed a novel framework to quantitatively infer community assembly mechanisms by phylogenetic bin-based null model analysis i.e., iCAMP."

Using the iCAMP framework, the researchers revealed new findings on the dynamic changes of ecological processes from 2009 to 2014 in grassland bacterial communities under long-term experimental warming.

"In simulated data, iCAMP shows outstanding performance in terms of precision, sensitivity, specificity, accuracy, and robustness," Zhou said. "Using iCAMP, we showed that climate warming increased homogeneous selection in soil bacterial community assembly, which was also related to the changes in drought and plant productivity."

Zhou adds that the general framework used in this study has potential to benefit not only microbial ecology, but also plant and animal ecology and that their findings have important implications for predicting and mitigating the ecological consequences of climate warming.

Widespread COVID-19 testing may be an obvious way to control an outbreak in a long-term care facility. But communication among the facility's staff, its residents and the residents' family members is crucial, too.

A new study led by Carl Shrader, a physician and researcher in the Department of Family Medicine in the West Virginia University School of Medicine, revealed the role that communication played in quashing a COVID-19 outbreak at Sundale, a long-term care facility in Morgantown.

"Timely communication was challenging and made more difficult by a lack of evidence-based information and widely circulating misinformation," said Shrader, who directs WVU's residency program. "There is a delicate balance between rapid dissemination of accurate information with the need for personal individual discussion in an unknown situation."

Shrader is also the medical director at Sundale, which was the epicenter of West Virginia's COVID-19 pandemic. From the first diagnosis of COVID-19 in a Sundale resident--in March--he took a leading role in the facility's response to the outbreak.

Before the facility was free of COVID-19, 52 residents and 19 staff members would be diagnosed with it. For five of those residents, the virus would prove fatal. But "despite the challenges of managing a COVID-19 outbreak in the absence of information, our facility's staff, families and leadership were able to work together to ensure limited viral spread and no change in the average monthly mortality at the facility," Shrader said.

He feels that early and widespread COVID-19 testing at the facility was key to keeping the infection rate low. As soon as the first cases came to light, the staff immediately tested all of the facility's hundred residents, whether or not they had symptoms of COVID-19. People who tested positive were separated from the other residents and housed in the same unit to prevent the virus from spreading.

Follow-up testing in the weeks that followed identified more residents who had the virus and confirmed when residents had gotten over it.

Because test kits were scarce early in the pandemic, not every staff member at Sundale could be swabbed for the virus. Fifty-six of the 162 staff members--mostly certified nursing assistants and licensed practical nurses--were chosen for testing because of their frequent contact with residents. All other facility staff members were directed to local drive-up testing sites.

"Maintaining availability of adequate staff in all divisions to ensure safe operation of the facility was high priority," Shrader said. "Clear communication about testing and staffing decisions was crucial in allaying fear and frustration."

Meeting with the staff members and explaining why some of them received the rapid test while others didn't alleviate staff members' concerns, prevented resentment from building and fostered the spirit of teamwork that makes good resident care possible.

Staff members weren't the only people who benefited from communication. So did residents' family members.

At first, the facility staff tried to keep family members informed by speaking to them over the phone, but they soon discovered that they couldn't keep up with the calls. There were simply too many people--with too many questions and concerns--to speak to them all individually.

Much of the information staff members were providing applied to multiple residents. So, with the residents' and family members' permission, they began using a version of Zoom that's compliant with medical-privacy laws to talk--and listen--to many family members at once.

Not only could the staff communicate with family members this way, but the family members could share information and build relationships with each other as well.

"Families, residents and staff bonded through this unique experience, and the creative use of technology to maintain open communication aided in this," said Courtney Pilkerton, an assistant professor of family medicine and member of the research team. "Zoom meetings continue to be popular, and many family members have requested that calls continue as they have found significant value in sharing their experiences with each other."

But communicating with one category of people was particularly difficult: residents with dementia.

"Living with dementia means a life revolving around a structured schedule," said Shauna Assadzandi, a medical resident at Sundale who was involved in the study. "Disruptions in that schedule can bring significant distress. If their son came every day to feed them lunch and dinner and now is not there, they may feel abandoned--not understanding why their son can no longer visit."

Staff at the facility had to pay special attention to those residents so they could spot psychosomatic symptoms--such as lack of appetite--and address them early. Just because some residents couldn't describe their feelings of loneliness, sadness or worry doesn't mean they weren't experiencing them.

"Older individuals--and, more specifically, those with dementia--don't always verbalize concerns, and it becomes crucial to watch for physical signs of distress, including weight change and intake of food and fluids," Assadzandi said.

"Much of our nursing staff has worked in the facility on the same unit for many years," she said. "They know the residents well and are often the first to notice small changes in behavior. These strong connections between staff and residents allow for more rapid and individual changes to care when needed."

A study conducted by researchers at São Paulo State University (UNESP) suggests that irisin, a hormone secreted from muscles in response to exercise, could have a therapeutic effect on COVID-19 patients. When they analyzed adipose cell gene expression, the researchers found that irisin modulated genes associated with replication of the novel coronavirus SARS-CoV-2 in human cells.

This finding was based on analysis of the transcriptome (all RNAs produced by genes) of adipose cells not infected by SARS-CoV-2 and treated with irisin. “We compared data for genes important in COVID-19 with our transcriptomic data to make correlations. The results offer a clue in the search for treatment of the disease during the emergency caused by the pandemic. It must be stressed that our findings are preliminary and merely suggest that irisin could have therapeutic potential in cases of COVID-19. Further research can pick up from here to see whether irisin’s effects on patients with the disease are indeed beneficial,” Miriane de Oliveira, a researcher at UNESP’s Medical School in Botucatu, São Paulo (Brazil), told Agência FAPESP.

An article describing the study is published in the journal Molecular and Cellular Endocrinology. The data were produced by Oliveira in postdoctoral research supported by FAPESP and focusing on the action of irisin and thyroid hormones in adipocytes.

The use of sequencing techniques enabled the researchers to identify 14,857 genes expressed in a subcutaneous adipose cell line. They observed alterations in gene expression when cells were treated with irisin.

Because of the pandemic, researchers decided to investigate the possible effects of irisin on genes associated with the replication of SARS-CoV-2. From data cross-tabulation, they discovered that treatment of adipocytes with irisin reduced expression of the genes TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10, which in turn regulate ACE-2, a key gene for viral replication because it encodes the protein to which the novel coronavirus binds in order to invade human cells.

Another positive finding was that irisin tripled levels of transcription of the gene TRIB3. Previous research has demonstrated the importance of maintaining expression of TRIB3. In fact, expression of TRIB3 is frequently diminished in older people, a factor that may be linked to augmented replication of SARS-CoV-2 and a higher risk of COVID-19 in this segment of the population.

“A third important point is the finding by other research groups that adipose tissue appears to serve as a repository for the virus,” Oliveira said. “This helps explain the higher risk of developing severe forms of the disease for individuals with obesity. In addition, obese people tend to have lower levels of irisin and higher levels of the receptor molecule used by the virus [ACE-2] than nonobese people” (read more at: agencia.fapesp.br/33729).

Produced endogenously during continuous exercise, irisin is known to be involved in the browning of adipose tissue. White fat stores energy in the form of triglycerides and lipids and can become inflamed. Brown fat breaks down blood sugar and fat molecules to create heat and help maintain body temperature. Thus, irisin is part of a calorie-burning process that can help treat metabolic disorders such as obesity. It is also known to modulate the activity of macrophages, which are immune cells that can release cytokines and trigger inflammation.

Data management

Oliveira’s study is an example of how managing data obtained in basic research can lay the foundation for other discoveries and research. “We began with a comparative analysis of the action of irisin and thyroid hormones in moderating fat accumulation and modulating genes in adipose cells,” she said. “The study produced a large amount of data, and with the advent of the pandemic and the discovery by other research groups of genes associated with replication of SARS-CoV-2, we decided to use our database to investigate how irisin [and thyroid hormones] may influence the disease.”

The original investigation set out to discover how these hormones perform their thermogenic role in reducing adipose tissue and generating energy in adipocytes. “We did this by means of transcriptomics to identify the genes affected by the hormones in question, and our findings served as a basis for the study relating to COVID-19,” Oliveira said.

This study showed that irisin not only moderates fat accumulation but also stimulates the expression of uncoupling protein 1 (UCP1), releasing heat and reducing fat deposits. Increased levels of UCP1 are compatible with decreased DNA damage and oxidative stress.

With this better understanding of the role played by irisin in obesity and possibly in COVID-19, the research group will now analyze its effect on cells infected with SARS-CoV-2. The principal investigator for this project is also Célia Regina Nogueira de Camargo, a professor in the Clinical Medicine Department of UNESP’s Botucatu Medical School. The project is supported by the Ministry of Education’s Coordination for the Improvement of Higher Education Personel (CAPES).

“The aim is to take another step in this line of research and determine whether the results obtained in our bioinformatics investigation can be confirmed in a three-dimensional adipose cell culture model,” Oliveira said. “We want to understand how irisin modulates the genes associated with SARS-CoV-2 replication.”

The article “Irisin modulates genes associated with severe coronavirus disease (COVID-19) outcome in human subcutaneous adipocyte cell culture” (doi: 10.1016/j.mce.2020.110917) by Miriane de Oliveira, Maria Teresa De Sibio, Lucas Solla Mathias, Bruna Moretto Rodrigues, Marna Eliana Sakalem and Célia Regina Nogueira can be retrieved from www.sciencedirect.com/science/article/pii/S0303720720302173.

Journal

Molecular and Cellular Endocrinology

DOI

10.1016/j.mce.2020.110917

Scientists from the CNRS, ENS-PSL, Inserm, and Sciences Po (1) revealed an increase in facial displays of trustworthiness in European painting between the fourteenth and twenty-first centuries. The findings, published in Nature Communications on 22 September 2020, were obtained by applying face-processing software to two groups of portraits, suggesting an increase in trustworthiness in society that closely follows rising living standards over the course of this period.

In having their portraits drawn, the greats of this world have sought, depending on the period, to display their power and inspire fear, or on the contrary to display a trustworthy appearance. Using their sources, historians had already perceived a shift toward greater trustworthiness over time, although these changes were difficult to document quantitatively.

To follow the historical evolution of interpersonal trust, a team of cognitive science researchers from the CNRS, ENS-PSL, Inserm and Sciences Po1 has created a facial analysis algorithm that can reproduce human judgements regarding the trustworthiness displayed by a face. To validate the algorithm, the scientists initially tested it on photographs of faces whose trustworthiness had already been rated by humans. During other tests, the algorithm reproduced the conclusions drawn from the scientific literature regarding the impact that factors such as age, gender, facial features or the emotions displayed have on the trustworthiness of a face.

By analysing a collection of 1,962 English portraits painted between 1506 and 2016 from the National Portrait Gallery in London, the authors observed that the number of facial cues connected to interpersonal trust increased over time. They also successfully reproduced their conclusions on 4,106 portraits from the Web Gallery of Art, which includes works from nineteen Western European countries between the years 1360 and 1918.

However, does this evolution reflect the transition of relatively violent societies into more cooperative ones? To validate this hypothesis, the algorithm was then applied to Selfiecity, a database including 2,277 photographic self-portraits posted on social media in six cities across the globe. The trustworthiness of faces was indeed correlated to the interpersonal trust and cooperation previously measured through international surveys.

In seeking the potential causes of this evolution, the team observed that increased trustworthiness in the portraits was more closely associated to increased per capita GDP than to institutional changes such as the emergence of more democratic institutions. The scientists are continuing this study on the basis of other sources, such as literary texts and musical production.

Boston, Mass. - A new review article from Beth Israel Deaconess Medical Center (BIDMC) shows people who are biologically male are dying from COVID-19 at a higher rate than people who are biologically female. In a review published in Frontiers in Immunology, researcher-clinicians at BIDMC explore the sex-based physiological differences that may affect risk and susceptibility to COVID-19, the course and clinical outcomes of the disease and response to vaccines.

"The COVID-19 pandemic has revealed a striking gender bias with increased mortality rates in men compared with women across the lifespan," said corresponding author Vaishali R. Moulton, MD, PhD, an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at BIDMC. "Apart from behavioral and lifestyle factors that differ between men and women, sex chromosome-linked genes, sex hormones and the microbiome control aspects of the immune responses to infection and are potentially important biological contributors to the sex-based differences we're seeing in men and women in the context of COVID-19."

Moulton and co-authors Nirupa Gadi, Samantha C. Wu and Allison P. Spihlman, all medical students in Moulton's laboratory at BIDMC, acknowledge that demographic differences between men and women predispose each group to risk in different ways. Men, for example, are more likely to smoke cigarettes, a known risk factor for severe COVID-19, and are more likely to have cardiovascular disease and hypertension, important underlying comorbidities in COVID-19; while women are more likely to hold jobs in health care, increasing their potential exposure to the virus.

Nonetheless, many animal and human studies demonstrate that females tend to mount stronger immune responses to infections than males, a trait that may be linked to increased susceptibility to inflammatory and autoimmune diseases. Reviewing the scientific literature regarding sex-based differences in cells of the immune system, X chromosome-linked genetics, sex hormones, the ACE-2 receptor and the microbiome, the scientists conclude that sex is a crucial yet understudied and often overlooked variable in research related to immunity and infectious disease.

"Vaccine-related research and clinical trials, including those currently underway for COVID-19, must include sex as a key variable when measuring and reporting outcomes," said Moulton, who is also an assistant professor of medicine at Harvard Medical School. "Understanding these factors will both help us better understand COVID-19 and guide the design of effective therapies and vaccine strategies towards sex-based personalized medicine moving forward."

Michigan Tech's Open Sustainability Technology (MOST) Lab developed three new open-source tools in response to COVID-19: a high-temperature 3D printer, a firefighter PAPR mask and a printable, emergency-use ventilator.

Today, with the evolution of digital manufacturing technologies such as 3D printers and circuit milling systems, humanity can share designs with others who can then replicate medical-grade devices for the cost of locally sourced materials. When the team began these studies last spring, personal protection equipment (PPE) was in short supply, most PPE was one-use and disposable, and the demand for hospital equipment was greater than supply. So the MOST Lab focused on a printer that could make reusable face masks, respiratory equipment that could be custom fit for firefighters and an inexpensive design for a 3D-printed ventilator.

Joshua Pearce leads the MOST Lab and is the Richard Witte Endowed Professor of Materials Science and Engineering and a professor of electrical and computer engineering. His team intentionally made open-source designs, which have been published in a special edition of HardwareX dedicated to COVID-19 technology.

"The nature of these designs is such that desired features are relatively easy to add with the test using protocols and parametric design files provided," Pearce said. "Our hope is that such devices can be built upon by others to achieve full regulatory approval in all countries to ensure humanity is prepared for the next pandemic."

Specs for the high-temp 3D printer Cerberus:

three-headed, self-replicating rapid prototyper (RepRap)

open-source and can be built for less than $1,000

200 degree Celsius-capable heated bed

500 degree Celsius-capable hot end

isolated heated chamber with 1 kilowatt space heater core with mains voltage chamber and bed heating for rapid start

prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively

Specs for the powered air-purifying particulate respirator (PAPR) for firefighters:

open-source and can be 3D-printed and assembled with widely available components for under $150, replacing commercial conversion kits (saving 85%) or proprietary PAPRs (saving over 90%)

parametric designs allow for adaptation to other core components and can be custom fit specifically to firefighter equipment, including their suspenders

controllable airflow and its design enables breathing even if the fan is disconnected or if the battery dies

meets National Institute for Occupational Safety and Health (NIOSH) airflow requirements for four hours, which is 300% over expected regular use

Specs for emergency-use ventilator:

open-source and can be 3D-printed for less than $170

resuscitation system based on open-source Arduino controller and 3D-printable parametric component-based structure

controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4

The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach.

Experimental results after testing on an artificial lung for peak inspiratory pressure (PIP), respiratory rate (RR), positive end-expiratory pressure (PEEP), tidal volume, proximal pressure, and lung pressure demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation.

Infants born to women with COVID-19 showed few adverse outcomes, according to the first report in the country of infant outcomes through eight weeks of age.

The study, led by researchers at UC San Francisco, suggests that babies born to mothers infected with the virus generally do well six to eight weeks after birth, however there was a higher rate of neonatal intensive care unit (NICU) admissions reported if the mothers had COVID-19 up to two weeks prior to delivery.

Among 263 infants in the study, adverse outcomes -- including preterm birth, NICU admission, and respiratory disease -- did not differ between those born to mothers testing positive for SARS-CoV-2 and those born to mothers testing negative. No pneumonia or lower respiratory tract infection were reported through eight weeks of age.

The study is published as a prepublication accepted manuscript in Clinical Infectious Diseases.

"The babies are doing well, and that's wonderful," said lead author Valerie J. Flaherman, MD, MPH, associate professor of pediatrics and of epidemiology and biostatistics at UCSF. "When coronavirus first hit, there were so many strange and unfortunate issues tied to it, but there was almost no information on how COVID-19 impacts pregnant women and their newborns. We didn't know what to expect for the babies, so this is good news."

The prospective study is part of a national project led by UCSF called PRIORITY (Pregnancy Coronavirus Outcomes Registry), which began in March 2020, shortly after the pandemic erupted in the United States. The project is designed for pregnant women with suspected or confirmed COVID-19, with the goal of better understanding how pregnant and postpartum women and their infants are affected by the virus.

It's known that pregnant women have alterations in their immune system that may increase the risk of severe illness from influenza viruses. In past outbreaks, women who contracted flu during pregnancy have been at higher risk for hospitalization, miscarriage or stillbirth, and their babies have had an increased likelihood of having birth defects.

While studies have reported that maternal SARS-CoV-2 infection increases the risk of preterm birth and can be transmitted from the mother to the infant, overall risks for the infants were not known and almost no information is available about how COVID-19 affects infants as they grow.

The new paper reports on live births among 179 mothers with a positive test for SARS-CoV-2 and 84 mothers who had a negative test. The births occurred at more than 100 U.S. hospitals. On average, the mothers were about 31 years old. Among women testing positive, 146 (81 percent) were symptomatic; among those testing negative, 53 (63 percent) were symptomatic.

Of the 263 infants in total, 44 were admitted to a NICU but no pneumonia or lower respiratory tract infections were reported during the study. Among the 56 infants assessed for upper respiratory infection, it was reported in two infants with COVID-positive mothers, and in one with a COVID-negative mother.

Among infants born to mothers who tested positive, the estimated incidence of a positive infant SARS-CoV-2 test was low at 1.1 percent, and COVID did not appear to impact those infants, the authors said.

"Overall, the initial findings regarding infant health are reassuring, but it's important to note that the majority of these births were from third trimester infections," said senior author Stephanie L. Gaw, MD, PhD, assistant professor of obstetrics, gynecology and reproductive sciences at UCSF. "The outcomes from our complete cohort will give the full picture of risks throughout pregnancy."

Two infants born to mothers who tested positive in the third trimester were reported to have birth defects, each with multiple congenital anomalies reported (one had cardiac, vertebral, renal and pulmonary anomalies, while the other had facial, genital, renal, brain and cardiac anomalies). One mother who tested negative reported an infant with gastrointestinal, renal and cardiac anomalies.

The researchers said the findings could help inform national and international guidelines and policies, but also noted some study limitations. Among those, tests for infection might be biased by false-positive or false-negative results. They also said that Latinas and Blacks were underrepresented in the study - in May, PRIORITY launched a new project to increase enrollment of underrepresented groups - and noted that further research is needed on infant incidence following maternal infection.

Researchers suggest employees should take a cue from Jimmy Fallon's Thank You Notes segment on The Tonight Show to improve workplace behavior. A recent University of Central Florida study suggests employees who keep a gratitude journal exhibit less rude behavior and mistreatment of others in the workplace.

"Gratitude interventions are exercises designed to increase your focus on the positive things in your life. One intervention involves writing down a list of things you are thankful for each day," says management Professor Shannon Taylor, who teamed up with fellow management Professor Maureen Ambrose and doctoral student Lauren Locklear for the study. "That simple action can change your outlook, your approach to work, and the way your co-workers see you."

Workplace mistreatment is widespread and can cost organizations millions of dollars each year. Bullying, gossip, and exclusion or ostracism have been shown to negatively impact physical health, job performance and job satisfaction. Mistreatment also hurts the bottom line, as it creates costs from productivity loss, employee turnover, and litigation.

"While organizations spend quite a bit of time and money to improve employee behavior, there are not a lot of known tools available to actually make the needed changes," Locklear said. "We found the gratitude journal is a simple, inexpensive intervention that can have a significant impact on changing employee behavior for the better."

For two weeks, study participants spent a few minutes a day jotting down the things, people and events they were grateful for -- and as a result, their coworkers reported that they engaged in fewer rude, gossiping, and ostracizing behaviors.

"Gratitude exercises are becoming increasingly popular products to improve employee attitudes and well-being, and our study shows managers can also use them to foster more respectful behavior in their teams," Taylor says.

The study was recently published in the Journal of Applied Psychology. Taylor, who joined UCF in 2012, has a doctorate in organizational behavior from Louisiana State University and a bachelor's degree in finance from Bradley University. His areas of research include leadership and workplace mistreatment. Ambrose is the Gordon J. Barnett Professor of Business Ethics at UCF College of Business. Her research interests include organizational fairness, ethics and workplace deviance. Locklear studies workplace deviance and mistreatment, as well as interventions in gratitude and mindfulness, and expects to graduate in the spring.

Researchers at the National Institute of Standards and Technology (NIST) have developed a new method of 3D-printing gels and other soft materials. Published in a new paper, it has the potential to create complex structures with nanometer-scale precision. Because many gels are compatible with living cells, the new method could jump-start the production of soft tiny medical devices such as drug delivery systems or flexible electrodes that can be inserted into the human body.

A standard 3D printer makes solid structures by creating sheets of material -- typically plastic or rubber -- and building them up layer by layer, like a lasagna, until the entire object is created.

Using a 3D printer to fabricate an object made of gel is a "bit more of a delicate cooking process," said NIST researcher Andrei Kolmakov. In the standard method, the 3D printer chamber is filled with a soup of long-chain polymers -- long groups of molecules bonded together -- dissolved in water. Then "spices" are added -- special molecules that are sensitive to light. When light from the 3D printer activates those special molecules, they stitch together the chains of polymers so that they form a fluffy weblike structure. This scaffolding, still surrounded by liquid water, is the gel.

Typically, modern 3D gel printers have used ultraviolet or visible laser light to initiate formation of the gel scaffolding. However, Kolmakov and his colleagues have focused their attention on a different 3D-printing technique to fabricate gels, using beams of electrons or X-rays. Because these types of radiation have a higher energy, or shorter wavelength, than ultraviolet and visible light, these beams can be more tightly focused and therefore produce gels with finer structural detail. Such detail is exactly what is needed for tissue engineering and many other medical and biological applications. Electrons and X-rays offer a second advantage: They do not require a special set of molecules to initiate the formation of gels.

But at present, the sources of this tightly focused, short-wavelength radiation -- scanning electron microscopes and X-ray microscopes -- can only operate in a vacuum. That's a problem because in a vacuum the liquid in each chamber evaporates instead of forming a gel.

Kolmakov and his colleagues at NIST and at the Elettra Sincrotrone Trieste, in Italy, solved the issue and demonstrated 3D gel printing in liquids by placing an ultrathin barrier -- a thin sheet of silicon nitride -- between the vacuum and the liquid chamber. The thin sheet protects the liquid from evaporating (as it would ordinarily do in vacuum) but allows X-rays and electrons to penetrate into the liquid. The method enabled the team to use the 3D-printing approach to create gels with structures as small as 100 nanometers (nm) -- about 1,000 times thinner than a human hair. By refining their method, the researchers expect to imprint structures on the gels as small as 50 nm, the size of a small virus.

Some future structures made with this approach could include flexible injectable electrodes to monitor brain activity, biosensors for virus detection, soft micro-robots, and structures that can emulate and interact with living cells and provide a medium for their growth.

"We're bringing new tools -- electron beams and X-rays operating in liquids -- into 3D printing of soft materials," said Kolmakov. He and his collaborators described their work in an article posted online Sept. 16 in ACS Nano.

Using a combination of demographic and clinical data gathered from seven weeks of COVID-19 patient care early in the coronavirus pandemic, Johns Hopkins researchers today published a "prediction model" they say can help other hospitals care for COVID-19 patients -- and make important decisions about planning and resource allocations.

Brian Garibaldi, M.D., associate professor of medicine at the Johns Hopkins University School of Medicine, led a team that published in the Annals of Internal Medicine the article that shares important lessons learned in the care of COVID-19 patients between March 4 and April 24, 2020, at five Johns Hopkins hospitals in Maryland and Washington, D.C.

During those 52 days, The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, Howard County General Hospital, Suburban Hospital and Sibley Memorial Hospital admitted a combined 827 people age 18 or older -- 336 Black, 264 white, 135 Hispanic, 48 Asian, 2 Native American and 42 multiracial -- who tested positive for the coronavirus and had symptoms of COVID-19.

From the data those patients generated, the researchers developed a prediction model using a set of risk factors known to be associated with COVID-19 to forecast how likely a patient's disease is to worsen while being treated in a hospital and at what point in their care that might happen. Among the risk factors researchers considered as part of the model were a patient's age, body mass index (BMI), lung health and chronic disease, as well as vital signs and the severity of a patient's COVID-19 symptoms at the time of admission.

The model, called the "COVID Inpatient Risk Calculator (CIRC)," is available online. Garibaldi says the calculator is meant to help hospital physicians and other health care providers assess the risk of a patient's condition worsening.

"This is some of what we've learned in the months since we started seeing patients with COVID-19 at our hospitals," says Garibaldi. "As we continue to grapple with high numbers of COVID-19 infections across the United States, it's important to share knowledge with our colleagues at other hospitals."

Among the highlights of the study was the rapidity with which the disease can progress from mild or moderate to severe, particularly if a patient had all or some of the risk factors associated with the disease. Forty-five of the patients in the study had severe COVID-19 when they were admitted to the hospital. But 120 patients developed severe disease or died within 12 hours of being admitted. Of the 302 patients in the study who developed severe disease or died, the median time of disease progression was 1.1 days.

"Rapid progression of disease following admission [to the hospital] provides a narrow window to intervene," Garibaldi writes in the article. "Different combinations of risk factors appear to predict severe disease or death, with probabilities ranging from over 90% to as little as 5%."

For example, using the CIRC, Garibaldi and his colleagues estimate that a 60-year-old white woman with a BMI of 28, no chronic disease and no fever who is hospitalized for COVID-19 has a 10% chance of her disease worsening by day two of her hospital stay. The longer she's in the hospital, the greater that chance becomes, at 15% after four days and 16% after a week.

Conversely, the researchers considered an 81-year-old Black woman admitted to the hospital with COVID-19. The hypothetical patient has a BMI of 35, diabetes, hypertension and a fever. CIRC forecasts her probability of progressing to severe disease or even death by just the second day of her hospital stay is 89%. That percentage increases to higher than 95% by days four and seven.

By June 24, 694 of the patients in the study had been discharged from the hospital, 131 had died and seven were still hospitalized with severe COVID-19.

"We identified a few readily measurable demographic and clinical factors that, when assessed on admission to the hospital, can predict if someone has a 5% or a 90% risk of developing severe disease or dying from COVID-19," says Amita Gupta, M.D., professor of medicine at the Johns Hopkins University School of Medicine, who directs the Center for Clinical Global Health Education and is a co-author of the study. "This is incredibly useful information to have when communicating with patients and their families, as well as for informing resource allocation in the hospital."

The study's data comes from a registry of all patients treated for the novel coronavirus infection at hospitals in the Johns Hopkins system. Known as "JH-CROWN," the registry -- which is funded by InHealth, the institution's precision medicine initiative -- offers demographics, diagnoses, procedures, social histories and other data points relevant to caring for COVID-19 patients.

"The JH-CROWN data registry embodies the same teamwork and dedication that went into the care of more than 3,000 COVID-19 patients admitted to Johns Hopkins hospitals since the start of the pandemic," Garibaldi says. "We hope it can teach us more about the nature of COVID-19 and improve both patient care and research as we prepare for a second wave of infections in the fall."

Diabetic ketoacidosis (DKA), a serious but common complication of type 1 diabetes, is linked to lower IQ scores and worse memory in children with type 1 diabetes, according to a study led by UC Davis Health researchers. The study published Sept. 22 in Diabetes Care is also the first large-scale work to differentiate between DKA's impact on children with a new diagnosis and children with a previous diagnosis of type 1 diabetes.

DKA happens when diabetes goes undiagnosed or is poorly managed. With DKA, blood sugar gets very high as acidic substances called ketones build up to dangerous levels in the body. Early signs of DKA include excessive thirst, frequent urination, and nausea, abdominal pain, weakness and confusion.

"We assessed the neurocognitive effects of DKA in children with known type 1diabetes as well as in those who were just diagnosed with it," said Simona Ghetti, professor of psychology at UC Davis and the lead author on the study. "Our study uncovered that even one severe episode of DKA in children newly diagnosed with type 1 diabetes is linked to cognitive problems; and among children with a previous diagnosis, repeated DKA exposure predicted lower cognitive performance after accounting for glycemic control."

The study included 376 children with type 1 diabetes and no DKA history and 758 children with type 1 diabetes and a history of DKA. These children, ages 6-18 years, were participating in a DKA clinical trial at the Pediatric Emergency Care Applied Research Network (PECARN) sites led by two of the study's co-authors, Nathan Kuppermann and Nicole Glaser.

One severe DKA episode can hurt memory and IQ

The study found that among children newly diagnosed with type 1 diabetes, those who experienced moderate and severe DKA had lower long-term memory compared to children with diabetes and no exposure to DKA. Greater severity of DKA was also associated with lower IQ in these children.

Children with a previous diagnosis showed lower performance compared with children with new onset in measures of memory and IQ, suggesting that cognitive deficits may worsen over time.

The study's large sample allowed the researchers to capture complex associations of DKA severity, socioeconomic status and glycemic control among previously diagnosed patients. These associations revealed that patients with repeated DKA exposure and poorly controlled type 1 diabetes are at substantial risk of cognitive deficits.

"The results from the study emphasize the importance of prevention of DKA in children with known type 1 diabetes and of timely diagnosis during new onset before the development of DKA," said Glaser, professor of pediatrics at UC Davis Health and senior author of the study. "There is an opportunity to prevent DKA with proper management of the glucose level in the blood."

Wave scattering appears practically everywhere in everyday life--from conversations across rooms, to ocean waves breaking on a shore, from colorful sunsets, to radar waves reflecting from aircraft. Scattering phenomena also appear in realms as diverse as quantum mechanics and gravitation. According to Pavel Ginzburg, professor at Tel Aviv University's School of Electrical Engineering, these phenomena become especially interesting when the waves in question encounter a moving object.

The everyday Doppler effect is familiar--witnessed as the audible shift in pitch that occurs, for example, as a fire engine's siren approaches, passes, and recedes. The idea that the observed frequency of a wave depends on the relative speed of the source and the observer, a popularized aspect of Einstein's theory of relativity, entails cosmic implications for the Doppler effect, particularly for light waves. Now, it appears that between relativity and the classical (stationary) wave regime, there exists another regime of wave phenomena, where memory influences the scattering process.

Memory effect alters the Doppler wave signature

As recently demonstrated by a team of scientists led by Ginzburg, including lead author Vitali Kozlov and coauthors Sergey Kosulnikov and Dmytro Vovchuk, the Doppler effect can be dramatically altered by memories of prior wave interactions. Specifically, when rotating dipoles are arranged to retain a long memory of past interactions with an incident wave, the Doppler signature displays asymmetric peaks in the scattered spectrum. Rather than fading quickly, these long-lasting past interactions affect the present and future evolution of the system under study.

"The newly discovered memory effect is universal," observes Ginzburg, "It can emerge in a variety of wave-related scenarios--from optics, where lasers are rotating molecules, to astronomy, where rotating dipoles can approximate neutron stars." Although the effect is universal, Ginzburg notes that not every scatterer possesses a long memory. "The effect is introduced on purpose, for instance with lumped circuitry in the case of electromagnetic applications," explains Ginzburg. He speculates that the memory effect may contribute to increased efficiency of radar target identification and classification, among other applications, such as stellar radiometry.

Ginzburg's team set out to answer the question of whether there is "an overlooked interaction regime, which on the one hand does not require relativistic velocities yet on the other hand cannot be straightforwardly explained with classical stationary physics." The team chose a simple case of a rotating dipole as a mathematical model that is "capable of describing properties of many real objects, such as quasars in astronomy or rotating blades of a helicopter in radar applications," according to Ginzburg.

The researchers hope that these newly demonstrated memory effects will be used to advance our understanding of the universe around us and help give rise to new technological applications that take advantage of long-memory materials to imprint motion signatures on scattered waves.

Hospitalized patients with COVID-19 may face an increased risk for kidney injury, a dreaded complication for those suffering from infection with the novel 2019 coronavirus, an observational study led by University of Michigan researchers has found.

According to Jochen Reiser, MD, PhD, the Ralph C Brown MD professor and chairperson of Rush's Department of Internal Medicine, patients with COVID-19 experience elevated levels of soluble urokinase receptor (suPAR), an immune-derived pathogenic protein that is strongly predictive of kidney injury.

"SuPAR is a circulating factor we've seen contribute to kidney injury in thousands of patients," Reiser said. "RNA viruses such as HIV and SARS-CoV-2 (the virus that causes COVID-19) elicit a suPAR response of the innate immune system, leading to a rise in blood suPAR levels. If there is a hyperinflammatory suPAR response, kidney cells may be damaged."

Reiser is an author of the multicenter study led by Salim Hayek MD, an assistant professor of cardiology at University of Michigan, "Soluble Urokinase Receptor in COVID-19 related Acute Kidney Injury." Published online in the Journal of the American Society of Nephrology on Sept. 22, the study results show that more than a third patients with COVID-19 end up in need of dialysis and are also at much higher risk of death.

The research team tested suPAR levels of 352 study participants when they were admitted to the hospital for COVID-19 infection. A quarter of the participants developed acute kidney injury while hospitalized, and their median suPAR levels were more than 60% higher than those of the rest of the participants.

The risk of needing dialysis was increased 20-fold in patients with the highest suPAR levels. Overall, median suPAR levels for these study participants hospitalized with severe COVID-19 were almost three times higher than levels of healthy people.

"Certainly, a suPAR level at time of hospitalization of COVID-19 patients will provide an important risk stratification tool with respect to patient outcomes such as intubation or kidney failure," Hayek said. "This will help hospitals by providing proper surveillance of patients at higher risk of a severe COVID-19 course.

"Now that we know the epidemiological link of suPAR to COVID-19-associated acute kidney injury (AKI), we must study if suPAR is a cause of COVID-19 associated AKI," Reiser said. "In other words, can AKI in COVID-19 infected patients be prevented by keeping plasma suPAR levels low? This hypothesis is supported by the findings of the paper showing that COVID-19 infected study patients with a suPAR level below 4.6 ng/ml never needed dialysis. A newly developed and specific suPAR apheresis device is about to enter a clinical pilot trial where this scenario is tested."