Culture

Bethesda, Maryland (March 5, 2020) -- The world is bracing for the impact of the novel coronavirus, COVID-19, which has now spread to over 30 countries, infecting more than 80,000 people with over 2,600 deaths globally. A better understanding of how this virus is transmitted is key to preventing its spread.

In two new papers published online in Gastroenterology, investigators from China describe the impact of coronavirus on the digestive tract. Key findings:

A significant portion of coronavirus patients have diarrhea, nausea, vomiting and/or abdominal discomfort before respiratory symptoms.

Researchers recommend monitoring patients with initial GI distress, which will allow for earlier detection, diagnosis, isolation and intervention.

Viral RNA is detectable in stool of patients with suspected coronavirus; it is now clear that the virus sheds into the stool.

Viral gastrointestinal infection and potential fecal-oral transmission can last even after viral clearance in respiratory tract.

Prevention of fecal-oral transmission should be taken into consideration to control the spread the virus.

Leesburg, VA, March 5, 2020--An article by radiologists from Wuhan, China--published open-access and ahead-of-print in the American Journal of Roentgenology (AJR)--concluded that chest CT had a low rate of misdiagnosis of COVID-19 (3.9%, 2/51) and could help standardize imaging features and rules of transformation for rapid diagnosis; however, CT remains limited for the identification of specific viruses and distinguishing between viruses.

Yan Li and Liming Xia at Tongji Hospital in Hubai Province studied the first 51 patients diagnosed with COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). In their retrospective cohort of 53 patients, as of February 9, a total of 99 chest CT examinations had been performed.

Comparing image reports of the initial CT study with laboratory test results to identify patterns suggestive of viral infection, according to Li and Xia, "COVID-19 was misdiagnosed as a common infection at the initial CT study in two patients with underlying disease and COVID-19."

Meanwhile, viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus.

As Li and Xia explained: "CT of one of the two patients with confirmed adenovirus infection showed ill-defined patchy ground-glass opacities (GGOs), segmental and subpleural consolidations in both lungs, and pleural effusion. CT of the other patient showed subpleural GGOs and consolidation with vascular enlargement, interlobular septal thickening, and air bronchogram sign."

The CT findings seen in Li and Xia's two adenovirus cases were similar to those observed in their COVID-19 cases.

The two authors also found CT features of COVID-19 that differ from both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV): a reversed halo sign in two patients (3.9%) and pulmonary nodules with a halo sign in nine patients (17.6%).

"These findings are not mentioned, to our knowledge, in the studies in the literature," the authors noted.

"It is valuable for radiologists to recognize that the CT findings of COVID-19 overlap with the CT findings of diseases caused by viruses from a different family, such as adenovirus, and have differences as well as similarities with viruses within the same family, such as SARS-CoV and MERS-CoV," added Li and Xia.

FAYETTEVILLE, Ark. - Caffeine increases the ability to focus and problem solve, but a new study by a University of Arkansas researcher indicates it doesn't stimulate creativity.

"In Western cultures, caffeine is stereotypically associated with creative occupations and lifestyles, from writers and their coffee to programmers and their energy drinks, and there's more than a kernel of truth to these stereotypes," wrote Darya Zabelina, assistant professor of psychology and first author of the study recently published in the journal Consciousness and Cognition.

While the cognitive benefits of caffeine -- increased alertness, improved vigilance, enhanced focus and improved motor performance -- are well established, she said, the stimulant's affect on creativity is less known.

In the paper, Zabelina differentiates "convergent" from "divergent" thinking. The former is defined as seeking a specific solution to a problem, for example, the "correct" answer. The latter is characterized by idea generation where a large set of apt, novel or interesting responses would be suitable. Caffeine was shown to improve convergent thinking in the study, while consuming it had no significant impact on divergent thinking.

For the study, 80 volunteers were randomly given either a 200mg caffeine pill, equivalent to one strong cup of coffee, or a placebo. They were then tested on standard measures of convergent and divergent thinking, working memory and mood. In addition to the results on creativity, caffeine did not significantly affect working memory, but test subjects who took it did report feeling less sad.

"The 200mg enhanced problem solving significantly, but had no effect on creative thinking," said Zabelina. "It also didn't make it worse, so keep drinking your coffee; it won't interfere with these abilities."

When immunologist Dr. Wei Cao joined Baylor College of Medicine three-and-a-half years ago, her first project was to investigate how inflammation contributes to Alzheimer's disease.

"Alzheimer's is the most common cause of dementia among older adults. The current understanding is that, in addition to having beta-amyloid plaques and tau protein tangles, the brains of patients with this condition have a marked inflammatory response, and that this inflammation might be more of a problem than protein aggregation itself," said Cao, associate professor of molecular and human genetics and the Huffington Center on Aging at Baylor.

Inflammation in Alzheimer's disease involves the activation of two types of cells in the brain: the resident immune cells called microglia, and astrocytes, star-shaped cells that support neuronal functions. In addition, there are elevated levels of cytokines, molecules that are produced by immune cells to promote inflammation. But the question remained, how does chronic inflammation in brains with Alzheimer's disease lead to neuronal dysfunction and the consequent neurodegeneration and dementia?

Zooming into the brain

Amyloid plaques in the brains of people with Alzheimer's disease have a heterogeneous composition; for instance, some may also contain sugars, lipids or nucleic acids. Previously, Cao and her colleagues found that amyloid fibrils with nucleic acids, but not those without them, triggered immune cells in the blood to produce type 1 interferon (IFN). IFN is a potent cytokine produced when immune cells sense nuclei acids, such as those that come from viral particles, in their environment. IFN triggers a beneficial inflammatory response that is the first line of defense against viral infections.

"While it is best known for its ability to induce an antiviral state in cells, IFN is also involved in immune modulation and tissue damage associated with infectious, autoimmune and other conditions. But, until now, IFN has not been explicitly implicated in Alzheimer's disease," Cao said.

"In this project, we focused on what was going on in brains with Alzheimer's disease," said Dr. Ethan R. Roy, a graduate student in the Graduate Program in Translational Biology and Molecular Medicine at Baylor while he was working on this project. "We began by investigating whether microglia from the brain were able to respond to the amyloid/nucleic acid combination by producing IFN."

Roy looked at multiple Alzheimer's mouse models in the lab of Dr. Hui Zheng, professor of molecular and human genetics and director of the Huffington Center on Aging, who also is co-principal investigator of the study. Roy found that almost all the animals' brains in these models had plaques containing nucleic acids. "The composition of these plaques had not been well characterized before," Roy said.

IFN leads the way to synapse loss

Interestingly, Cao, Roy and their colleagues found that the same mouse brains that had amyloid plaques with nucleic acids also showed a molecular signature mimicking an antiviral IFN response. Further experiments revealed that nucleic acids in the plaques activated brain microglia, which produced IFN that in turn triggered a cascade of inflammatory reactions that led to the loss of synapses, the junctions between neurons through which they communicate. Synapse loss is a key part of neurodegeneration and can lead to memory loss and eventually dementia.

It is well known that synapse loss is directly mediated by the complement system, which is part of the immune system. It comprises a group of proteins that work together to clear microbes and damaged cells, but it also is involved in inflammation.

"Although we knew that complement activation triggered synapse loss, what we discovered was the chain of events that led to this outcome. The chain of events points to IFN-mediated pathways controlling complement activation," Cao said. "We found that blocking the IFN-triggered cascade of reactions significantly dampened microglia activation and reduced synapse loss in our mouse models, further supporting the leading role of IFN in this process."

This study provides a major advance in the understanding of a process that leads to neuronal damage, by connecting IFN, complement and synapse loss: IFN controls the expression of multiple components of the complement cascade and mediates synapse elimination in a complement-dependent manner.

Human connection

The researchers looked into human brains with Alzheimer's disease to see if they presented with characteristics that were similar to those they had observed in mouse models of the condition.

"We found that human brains with Alzheimer's disease have profound activation of the IFN pathway, suggesting that mechanisms similar to the one we found in mice may be involved in neuronal destruction in people with the disease," Roy said. "Further studies need to be conducted to evaluate this hypothesis."

This is important because it would lead to a better understanding of how the disease occurs and suggest novel therapies for this incurable disease.

The accumulation of amyloid plaques in human brains is known to poorly correlate with the severity or duration of dementia. There are people without signs of dementia who harbor significant amounts of both amyloid plaques and tau tangles in their brains, but remarkably lack the robust microglial activation and inflammatory response that is associated with loss of synapses and neurons. On the other hand, the brains of people with dementia linked to Alzheimer's disease present with amyloid plaques, tau tangles and inflammation that is involved in neurodegeneration.

"Our findings in mouse models suggest that it is plausible that plaques that accumulate in Alzheimer's disease patients and those in non-demented individuals differ in their content of nucleic acids. It is thus of great interest to examine more closely the molecular constituents of amyloid plaques in the brains of cognitively resilient individuals and compared them to those of Alzheimer's disease cases," Cao said.

This work also may provide new insights into the aging brain. Other work has shown that IFN also seems to participate in the normal aging process of the brain. Cao, Roy and their colleagues think it is also worthwhile to further explore the possibility of modulating IFN activity in aging populations.

CLEVELAND--Scientists at Case Western Reserve University are using Artificial Intelligence (AI) to reveal apparent cellular distinctions between black and white cancer patients, while also exploring potential racial bias in the rapidly developing field of AI.

Their most recent published research asserts that AI analysis of digitized images of cancer tissues reveals critical variations between black and white male prostate cancer patients. The work also suggests the new population-specific information--in addition to image detail on tissue slides also analyzed by computers--could substantially improve care for black patients with prostate cancer.

"On one level, we're simply trying to understand and answer this question: 'Are there biological differences in the disease, in the cancer, that are a function of your ethnicity or your race?'" said Anant Madabhushi, the F. Alex Nason Professor II of Biomedical Engineering at Case Western Reserve and senior author on a study published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. "In other words, is there something else going on that can't be explained by other disparities- The answer appears to be, 'yes.'"

This new work on prostate cancer builds on mounting evidence that clear biological differences between races can be discovered at a cellular level in the analysis of cancer cells--information which can be useful to tailor medical care to specific groups and individuals within those populations.

$3.2M in three new grants from the Department of Defense

Madabhushi and his lab, along with collaborators from the Case Western Reserve School of Medicine, University of Washington Seattle and Perelman School of Medicine at the University of Pennsylvania, have also been awarded $3.2 million in three grants from the U.S. Department of Defense to assess biological differences in prostate and breast cancers between black and white patients:

Sanjay Gupta, Carter Kessell Associate Professor of Urology at the Case Western Reserve School of Medicine and Madabhushi were awarded $1.6 million to study how AI might be used to explore differences at the morphologic and molecular level of prostate cancer between black and white men.

Madabhushi, Jonathan Liu at the University of Washington-Seattle and Dr. Priti Lal at the Perelman School of Medicine at the University of Pennsylvania were awarded $1 million to develop new approaches to understand biological differences between prostate cancer appearance in black and white men. The grant will involve a new technique pioneered by Liu's group called "light sheet microscopy tissue imaging," which uses AI and 3D technology to view tumors in an entirely new way, Madabhushi said.

Cheng Lu, an assistant research professor in Madabhushi's Center for Computational Imaging and Personalized Diagnostics, and collaborators, were awarded a three-year $570,000 grant to use AI to study differences in appearance of tissue biopsy images of triple-negative breast cancer, a very aggressive form of breast cancer, between black and white women.

Implicit in all of the ongoing research, Madabhushi said, is the larger question about whether the racial differences being discovered at the cellular level are revealing a research bias at the human level.

"Even as we do this groundbreaking research, we can't allow ourselves to get trapped into trusting these models blindly," he said, "so we need to question whether we are considering all populations (and) ask how diverse our research pool is."

Prostate cancer study

Racial differences were a key component in the most recent research work. The prostate cancer study was performed over three years at six sites and involved nearly 400 men with the disease.

One of the critical questions in management of prostate cancer patients is to identify which men following prostate surgery are at higher risk of disease recurrence and could benefit from adjuvant therapy.

The patient pool in this study, however, was about 80% white and 18% black, "so the model was biased toward the majority population," Madabhushi said. "Once we found the variations, applying the model to all would be doing a disservice to that one population."

Once researchers created a race-specific model, the accuracy in determining which black patients would have a recurrence of the cancer increased six-fold, Madabhushi said.

Like previous cancer research led by Madabhushi's lab, the scientists asked the computer to look for patterns not only from images of the tumor itself, but at tissue outside the tumor, known as the stroma.

In doing so--in this and other cancer studies--they have been able to successfully tell, among other things, which patients would respond well to chemotherapy, immunotherapy or even, in some cases, whether cancer would return or how long a patient might live.

Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States and one of the leading causes of cancer death among men of all races, according to the Centers for Disease Control.

Further, while surgical resection of the prostate--known as a radical prostatectomy--is performed for about 75,000 newly diagnosed patients each year, 30% to 40% will see the cancer return, Madabhushi said.

In this case, armed with the knowledge of which patients had a recurrence of the cancer, scientists were able to retroactively see visual signals in tissue slides from their initial diagnosis to determine which patients would suffer that recurrence.

Lead authors who collaborated with Madabhushi on the paper included Hersh Bhargava, a PhD student at the University of California-San Francisco and Patrick Leo, a graduate student of biomedical engineering at Case Western Reserve University.

Additional quotes:

Sanjay Gupta, Carter Kessell Associate Professor of Urology at the Case Western Reserve School of Medicine: "The major goal of this application is to address the aspect of health disparity in prostate cancer by constructing a race-specific prostate cancer classifier for prognostic prediction and risk assessment. The proposal utilizes a novel suite of computerized image analysis and computer vision tools to quantify histomorphometric features of tumor along with the expression of a panel of biomarkers differentially expressed in race-specific prostate cancer. "

Lead author Hersh Bhargava, a PhD student at the University of California -San Francisco said the researchers were able to "look at, and actually measure, hundreds of thousands, even millions, of cancer cells to see features that a human could never see--including structural characteristics."

"It's clear from the existing scientific literature that there are racial disparities in all cancers, but it appears that especially in prostate cancer that those differences can't be explained by access to care or socioeconomic status--but rather that there is a biological component to how the cancers manifest differently between black and white patients."

Patrick Leo, a Case Western Reserve graduate student, author on the paper and researcher in Madabhushi's lab, said that the research was focused on a population-disparities element that has not been recognized until now in what he called the "AI-for-health space."

"We know now that the risk is that if you just build a model for all patients, you will actually perform worse for patients in the minority and that's something we cannot accept, even if it's not something we did intentionally. So, if you want a model to work on patients from all populations, you have to deliberately include a population-specific aspect."

A new joint study by Tel Aviv University (TAU) and Weizmann Institute of Science researchers has yielded an innovative method for bolstering memory processes in the brain during sleep.

The method relies on a memory-evoking scent administered to one nostril. It helps researchers understand how sleep aids memory, and in the future could possibly help to restore memory capabilities following brain injuries, or help treat people with post-traumatic stress disorder (PTSD) for whom memory often serves as a trigger.

The new study was led by Ella Bar, a PhD student at TAU and the Weizmann Institute of Science. Other principal investigators include Prof. Yuval Nir of TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience, as well as Profs. Yadin Dudai, Noam Sobel and Rony Paz, all of Weizmann's Department of Neurobiology. It was published in Current Biology on March 5.

"We know that a memory consolidation process takes place in the brain during sleep," Bar explains. "For long-term memory storage, information gradually transitions from the hippocampus -- a brain region that serves as a temporary buffer for new memories -- to the neocortex. But how this transition happens remains an unsolved mystery."

"By triggering consolidation processes in only one side of the brain during sleep, we were able to compare the activity between the hemispheres and isolate the specific activity that corresponds to memory reactivation," Prof. Nir adds.

Bar says, "Beyond promoting basic scientific understanding, we hope that in the future this method may also have clinical applications. For instance, post-traumatic patients show higher activity in the right hemisphere when recalling a trauma, possibly related to its emotional content.

"The technique we developed could potentially influence this aspect of the memory during sleep and decrease the emotional stress that accompanies recall of the traumatic memory. Additionally, this method could be further developed to assist in rehabilitation therapy after one-sided brain damage due to stroke."

The researchers began from the knowledge that memories associated with locations on the left side of a person are mostly stored in the right brain hemisphere and vice versa. While exposed to the scent of a rose, research participants were asked to remember the location of words presented on either the left or right side of a computer screen. Participants were then tested on their memory of the word locations, then proceeded to nap at the lab. As the participants were napping, the scent of roses was administered again, but this time to only one nostril.

With this "one-sided" odor delivery, the researchers were able to reactivate and boost specific memories that were stored in a specific brain hemisphere.

The team also recorded electrical brain activity during sleep with EEG. The results showed that the "one-sided" rose scent delivery led to different sleep waves in the two hemispheres. The hemisphere that received the scent revealed better electrical signatures of memory consolidation during sleep. Finally, in the most crucial test of all, subjects were asked after waking up to undergo a second memory test about the words they had been exposed to before falling asleep.

"The memory of the subjects was significantly better for words presented on the side affected by smell than the memory for words presented on the other side," Bar says.

"Our findings emphasize that the memory consolidation process can be amplified by external cues such as scents," she concludes. "By using the special organization of the olfactory pathways, memories can be manipulated in a local manner on one side of the brain. Our finding demonstrates that memory consolidation likely involves a nocturnal 'dialogue' between the hippocampus and specific regions in the cerebral cortex."

The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health. Recent studies have linked the gut microbiome with several beneficial properties, such as aiding in the development of our immune system and warding off pathogen infections.

Many deadly pathogens are motile, meaning they can move spontaneously, and their ability to infect is based on their response to different environmental cues. Major cues for the pathogens are the molecules (or metabolites) produced in the gut. Pathogens interpret distinctive metabolites differently and are either attracted or repelled by them (i.e., migrate toward or away from them).

The metabolite indole is an example of a microbiome-produced small molecule that is abundant in the gut and is a powerful repellent for bacteria. According to Dr. Pushkar Lele, assistant professor, and Dr. Arul Jayaraman, professor, in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, this fact led to a simple question: "Why does indole - which is produced by many of our beneficial bacterial species - not repel the good gut bacteria along with the bad ones?"

To answer this question, a research team including Lele, Jayaraman and Dr. Michael Manson from the Department of Biology at Texas A&M, studied the response of the beneficial gut bacteria, E. coli to indole. In an article in the Proceedings of the National Academy of Sciences, the researchers describe the discovery of a previously unknown response to indole, in which the molecule seems to both repel and attract bacteria. This Janus response - named after the Roman god Janus who had two faces, one looking into the future and one looking into the past - has to do with the way indole is interpreted by the bacterial chemo-receptors.

"We found that there are two receptors in E. coli that sense indole," Lele said. "One senses indole as a repellent, and one senses indole as an attractant. Sustained exposure to high concentrations of indole desensitizes the receptor that interprets it as a repellent. This leads to indole being sensed only as an attractant."

According to Jayaraman, the Janus response displays a large amount of sophistication, and the discovery could lead to a better understanding of the complexities of the gut microbiome. "Beneficial bacteria aggregate on the surfaces within the gut based on some common feature," said Jayaraman. "We propose that one such feature is the ability to produce or sense indole. Bacteria that produce indole could group together and be attracted to niches where indole concentrations are high."

Since the bacteria that produce indole in the gut typically are enmeshed in mucus layers among other bacteria, the indole concentration drops as one gets further away from the source of indole. Since pathogens tend to pass through the gut relatively far from the bacteria that produce indole, they are not likely to encounter high concentrations of indole for a sustained period. Therefore, they are not sensitized to indole, and any indole they encounter repels them.

Studies continue to show that it is important to have a diverse mix of beneficial bacteria in the gut. According to Lele, this research is a step toward understanding how the gut microbiome might change with time. "The key question is, 'How do different species of bacteria colonize specific niches?' We have addressed a part of that question," said Lele. "The next step is to examine the response of multiple species of bacteria to a mix of different metabolites that are found in the gut."

A population of stem cells with the ability to generate new bone has been newly discovered by a group of researchers at the UConn School of Dental Medicine.

In the journal STEM CELLS, lead investigator Dr. Ivo Kalajzic, professor of reconstructive sciences, postdoctoral fellows Dr. Sierra Root and Dr. Natalie Wee, and collaborators at Harvard, Maine Medical Research Center, and the University of Auckland present a new population of cells that reside along the vascular channels that stretch across the bone and connect the inner and outer parts of the bone.

"This is a new discovery of perivascular cells residing within the bone itself that can generate new bone forming cells," said Kalajzic. "These cells likely regulate bone formation or participate in bone mass maintenance and repair."

Stem cells for bone have long been thought to be present within bone marrow and the outer surface of bone, serving as reserve cells that constantly generate new bone or participate in bone repair. Recent studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow, but no research has proved the existence of cells within these channels that have the ability to form new bones.

In this study, Kalajzic and his team are the first to report the existence of these progenitor cells within cortical bone that can generate new bone-forming cells - osteoblasts - that can be used to help remodel a bone.

To reach this conclusion, the researchers observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant, and began to reconstruct the bone marrow cavity and form new bone.

While this study shows there is a population of cells that can help aid bone formation, more research needs to be done to determine the cells' potential to regulate bone formation and resorption.

EAST LANSING, Mich. - Individuals in the LGBT community face stressors that have dire consequences on their health. Researchers from Michigan State University are the first to pinpoint social factors that can reduce these stressors and improve health for LGBT people.

"When we reviewed past studies, we found a pretty stark bias toward studying what made things worse," said William Chopik, assistant professor of psychology at MSU and lead author. "That's really important research, but there are plenty of positive parts of people's lives that might disrupt some of the more stressful ones."

Chopik surveyed 2,560 LGBT adults and discovered that surrounding yourself with a large social network - particularly with people who share your sexual identity - reduced the harmful effects of discrimination on health. Specifically, participants measured their perceived discrimination, stress and social network size, as well as their physical health, depression and life satisfaction.

"Having more family and friends around gives us more people to depend on when we really need it. When it comes to discrimination, people want someone they can rely on who can provide a listening ear," Chopik said. "A lot of the time, this means giving emotional support, so having a larger social network makes that possible."

The surprising finding, Chopik said, related to who specifically made up one's network. The number of straight individuals in a network didn't make a difference in improving health; rather, having more LGBT friends and family around was the most beneficial for those in the LGBT community. Additionally, ages of people in a network did not matter, so long as they shared an identity.

Chopik believes that the research, published in the Journal of Health and Aging, underscores how important a person's background is for their health and well-being.

"People experience all sorts of stress every day and the ability to cope with it effectively can prevent a major health crisis," Chopik said. "For LGBT people, we found that social networks were a resource they could rely on for support."

Many people who face ongoing discrimination shut down their relationships or isolate themselves, Chopik said. But for LGBT people, the larger the social circle, the better.

Additionally, Chopik hopes that the findings reinforce for medical professionals the importance of considering their patients' psychological stress.

"Oftentimes, many in the medical community are agnostic about the repeated stressors that LGBT people face every day," Chopik said. "We found that the stress that arises from discrimination predicts worse physical and mental health. Having a better understanding of the risk and protective factors present in their patients' environments can lead to a more holistic understanding of their health and well-being."

HOUSTON - (March 5, 2020) - Molecule-sized drills do the damage they are designed to do. That's bad news for disease.

Scientists at Rice University, Biola University and the Texas A&M Health Science Center have further validation that their molecular motors, light-activated rotors that spin up to 3 million times per second, can target diseased cells and kill them in minutes.

The team led by Biola molecular biochemist Richard Gunasekera and Rice chemist James Tour showed their motors are highly effective at destroying cells in three multicellular test organisms: worms, plankton and mice.

A study in the American Chemical Society journal ACS Applied Materials & Interfaces shows the motors caused various degrees of damage to tissues in all three species. The journal plans to designate the paper as an open-access ACS Editors' Choice.

The project's original goal was to target drug-resistant bacteria, cancer and other disease-causing cells and destroy them without damaging adjacent healthy cells. Tour has argued cells and bacteria have no possible defense against a nanomechanical drilling force strong enough to punch through their walls.

"Now it has been taken to a whole new level," Tour said. "The work here shows that whole organisms, such as small worms and water fleas, can be killed by nanomachines that drill into them. This is not just single-cell death, but whole organism, with cell death in the millions.

"They can also be used to drill into skin, thereby suggesting utility in the treatment of things like pre-melanoma," he said.

The researchers saw different effects in each of the three models. In the worm, C. elegans, the fast motors caused rapid depigmentation as the motors first caused nanomechanical disruption of cells and tissues. In the plankton, Daphnia, the motors first dismembered exterior limbs. In both cases, after a few days, most or all of the organisms died.

For mouse models, researchers applied the nanomachines in a topical solution to the skin. Activating the fast motors caused lesions and ulcerations, demonstrating their ability to function in larger animals.

"That mouse skin changes due to the 'drilling' by the nanomachines might be the one of most interesting aspects of the study to scientists," said Gunasekera, an adjunct faculty member and former visiting scientist at Rice and currently associate dean and a professor of biochemistry at Biola. He is co-lead author of the paper with Thushara Galbadage, an associate professor of public health at Biola.

"It could mean direct topical treatment to skin conditions such as melanomas, eczema and other skin diseases," Gunasekera said. "This paper is significant because it's the first testing of nanomachines where we've proven its effectiveness in vivo. All other studies done so far were done in vitro."

He suggested the motors could be used for therapeutic parasite control as well as local treatment of such diseases as skin cancer.

Researchers from the Hubrecht Institute (KNAW) developed a new method to assess how production and degradation of gene transcripts are regulated. In this study, published in Science on the 6th of March, they found that cells use distinct strategies to control the number of transcript copies, which is required for the cell to function properly.

Our bodies consist of trillions of cells that all contain the same DNA. Even though the DNA in each cell is the same, we consist of many different cell types, each with different functions. In different cell types, different sets of genes on the DNA are active - different recipes are being used to build the components of the cell. This in turn determines what kind of cell it is, for instance a skin cell or a muscle cell. To do this, the cell makes copies of the genes, so-called transcripts, that can be used to produce proteins.

Balancing creation and destruction

The number of transcripts of each gene in a cell is a measure of the activity of these genes. This number can be influenced by making new copies, a process called transcription, and by destroying already existing copies, a process called degradation. In individual cells, the number of transcript copies is typically measured by breaking up the cell and thus cannot be followed over time in the same cell. Until now it was therefore unclear how a combination of transcription and degradation in a single cell regulates the number of copies of a particular transcript.

Labeling new copies

Researchers from the groups of Alexander van Oudenaarden, Hans Clevers and Marvin Tanenbaum at the Hubrecht Institute set out to solve this problem by developing a new single-cell sequencing technique to distinguish freshly made transcripts from pre-existing transripts.

Distinct strategies

By combining these data with computer models, the researchers could figure out that both transcription and degradation are heavily involved in regulating the number of copies of a transcript. Battich: "Cells seem to use distinct strategies to regulate the activity of their genes - or the number of copies of these transcripts. For some genes, the cell has to be able to very quickly change the number of copies. Those genes were both being transcribed and degraded at high levels. By involving both processes, cells were able to change the number of copies very quickly, for instance by decreasing transcription and increasing degradation simultaneously."

The new method, called scEU-seq, can be used to study a plethora of processes, such as the specialization of cells during development, the regulation of cell division in healthy and cancer systems.

As the ice sheet covering most of Greenland retreats, Florida State University researchers are studying the newly revealed landscape to understand its role in the carbon cycle.

FSU researchers Anne Kellerman, a postdoctoral researcher in the Department of Earth, Ocean, and Atmospheric Science, and Associate Professor Robert Spencer explored the composition of dissolved organic carbon in the lakes and streams on the island and found that the newly thawed landscape was feeding these bodies of water with rich carbon sources. This dissolved organic carbon that forms the basis of the microbial food web was then degraded by the intense sunlight that comes during the summer months in Greenland. Their findings were published in Limnology and Oceanography .

Knowing that the landscape is an important driver of the carbon found in the lakes affects the predictions scientists make about the future of the climate there and the types of life these environments may support.

"This was a first step toward making projections as the ice sheet retreats in Greenland, and what that means for carbon cycling, especially in aquatic environments in the region," Spencer said.

The lakes the researchers studied have high organic carbon concentrations, which typically are found in bodies of water with darker coloration, such as the swamps that are found throughout much of Florida. But the water in these Arctic lakes is optically much clearer than would be expected with the high organic carbon concentrations. The same scenario has been described in other arid regions that receive lots of sunlight.

Robert Spencer, associate professor of oceanography in the Department of Earth, Ocean, and Atmospheric Science

"You have this atypical situation, where you have these high organic carbon concentrations, and we're interested in what's causing that and if it's going to stay that way or how it may change," Kellerman said. "As it stands today, I don't know that we necessarily know the definitive answer to that yet, but what we have done is provide a possible explanation for this scenario."

After collecting samples, researchers used an ultrahigh resolution mass spectrometer at the FSU-headquartered National High Magnetic Field Laboratory to investigate the tens of thousands of individual organic molecules observed in each water sample.

"Different types of organic matter play different roles in the environment, and they also can degrade by different processes and at different rates," Kellerman said. "Some parts of the carbon pool are relatively resistant to degradation and might eventually end up as a long-term carbon store."

Dissolved organic matter is a major part of the global carbon pool. As more land is exposed in a warming Arctic, questions about the source of that matter and its implications for carbon cycling become more important.

"Since we've had advanced scientific research on Earth, we've not had environments like that which we are seeing opening up every year in the Arctic," Spencer said. "It's changing very, very quickly. So it's posing all these questions in rapid succession."

The conventional scientific process for identifying bacteria’s family – known as serotyping – can be time consuming. For salmonella, it used to take three days, and in some cases more than 12 days to assign a final classification for complex servovars.

Researchers from Cornell, the Mars Global Food Safety Center in Beijing, and the University of Georgia have developed a method for completing whole-genome sequencing to determine salmonella serotypes in just two hours and the whole identification process within eight hours.

heir research was published Feb. 24 online in the journal Food Microbiology.

Determining salmonella’s serotype makes it easier for food safety sleuths to find the source of bacterial contamination, which can occur in a wide range of foods, such as fruits, vegetables, nuts, meat, cereal, infant formula and pet food.

“As the food supply chain becomes ever more global and interconnected, the opportunity for food to become contaminated with salmonella increases,” said lead author Silin Tang, Ph.D. ’15, senior research scientist in microbial risk management at the Mars Global Food Safety Center in China. “In the fast-moving world of food manufacturing, where rapid identification and response to salmonella contamination incidents is critical, developing a more efficient pathogen identification method is essential.”

Conventional serotyping has been at the core of public health monitoring of salmonella infections for a half-century, Tang said. But long turnaround times, high costs and complex sample preparations have led global food safety regulators, food authorities and public health agencies to change to whole-genome sequencing methods for pathogen subtyping.

All 38 salmonella strains – representing 34 serotypes – assessed in this study were accurately predicted to the serotype level using whole-genome sequencing.

This is important news for the food industry, as very few laboratories can conduct classical serotyping, said Martin Wiedmann, Ph.D. ’97, the Gellert Family Professor in Food Safety and a Cornell Institute for Food Systems faculty fellow.

“In some countries,” Wiedmann said, “it can take up to two days to even get the suspected salmonella to a certified lab.”

With whole genome sequencing, he said, the new state-of-the-art test relies on simple equipment. “For the food industry, processing plants are in the middle of nowhere,” he said. “Now you can conduct testing in a lab that’s close to the food processing plant.”

In the United States, salmonella bacteria cause approximately 1.3 million infections, more than 26,000 hospitalizations and more than 400 deaths annually, according to annual estimates from the U.S. Centers for Disease Control and Prevention.

Different salmonella serotypes often come from different places, said Wiedmann, who explained the process through an example: chicken pot pie.

“Where does the salmonella come from?” he said. “You have carrots, peas, obviously chicken, and spices. If you have salmonella enteritidis – that’s usually associated with chicken – then you look for and track down the source of the chicken. If you have salmonella virchow, the serotype usually associated with food in southeast Asia, then you want to track down the spices from there. … Serotyping provides food safety scientists with a priority list of where to look.”

In addition to Silin and Wiedmann, the other researchers on the study, “Evaluation of Real-Time Nanopore Sequencing for Salmonella Serotype Prediction,” are Feng Xu, Chongtao Ge, Hao Luo, Guangtao Zhang, Abigail Stevenson and Robert C. Baker of the Mars Global Food Safety Center; and Shaoting Li and Xiangyu Deng of the University of Georgia. Funding was provided by the Mars Global Food Safety Center.

Journal

Food Microbiology

DOI

10.1016/j.fm.2020.103452

Google is racing to develop quantum enhanced processors that utilize quantum mechanical effects to one day dramatically increase the speed at which data can be processed.

In the near term, Google has devised new quantum enhanced algorithms that operate in the presence of realistic noise. The so called quantum approximate optimisation algorithm, or QAOA for short, is the cornerstone of a modern drive towards noise-tolerant quantum enhanced algorithm development.

The celebrated approach taken by Google in QAOA has sparked vast commercial interest and ignited a global research community to explore novel applications. Yet, little actually remains known about the ultimate performance limitations of Google's QAOA algorithm.

A team of scientists, hailing from Skoltech's Deep Quantum Laboratory, took up this contemporary challenge. The all-Skoltech team led by Prof. Jacob Biamonte discovered and quantified what appears to be a fundamental limitation in the wildly adopted approach initiated by Google.

Reporting in Physical Review Letters, the authors detail the discovery of so called reachability deficits - the authors show how these deficits place a fundamental limitation on the ability of QAOA to even approximate a solution to a problem instance.

The Skoltech team's findings report a clear limitation of the variational QAOA quantum algorithm. QAOA and other variational quantum algorithms have proven extremely difficult to analyse using known mathematical techniques due to an internal quantum-to-classical feedback process. Namely, a given quantum computation can only run for a fixed amount of time. Inside this fixed time, a fixed number of quantum operations can be executed. QAOA seeks to iteratively utilize these quantum operations by forming a sequence of increasingly optimal approximations to minimize an objective function. The study places new limits on this process.

The authors discovered that QAOA's ability to approximate optimal solutions for any fixed depth quantum circuit is fundamentally dependent on the problems "density." In the case of the problem called MAX-SAT, the so called density can be defined as the ratio of the problems constraints to variable count. This is sometimes called clause density.

The authors discovered problem instances of high density whose optimal solutions cannot be approximated with guaranteed success, regardless of the algorithms' run-time.

Few studies to date have evaluated patient experiences with payer-based CareFirst Patient-Centered Medical Home (PCMH) programs. The CareFirst BlueCross Blue Shield PCMH program aims to improve health care services, particularly for patients with multiple chronic conditions. It includes nurse care coordinators and individualized patient care plans.

“Patients with multiple chronic conditions are at an increased risk for hospitalization, and need additional coordination of care, and have high health care costs,” explains Dr. Debora Goetz Goldberg, who led the study at George Mason University’s College of Health and Human Services.

Goldberg and colleagues found that payer-based patient-centered medical home models with enhanced care coordination may be beneficial to patients with multiple chronic illness. Patients who completed their care plans had more positive experiences than those who did not. This suggests the care plan is key to the success of this model. Nurse care coordinators—who work closely with patients on developing the care plan and meeting individual goals—also played an important role in the program.

“Individuals with multiple chronic conditions often do not have their needs met in traditional primary care settings,” explains Goldberg. “Alternative models of care, such as the CareFirst PCMH, are approaches providers are experimenting with to improve the quality of care for these patients.”

In addition to improving health care quality, PCMH aims to slow rising health care costs over time. The program functions by focusing on the relationship between patients and their primary care provider.

For the study published in Population Health Management, Goldberg and colleagues surveyed 1,308 adults from 2015-2017. This study was supported by a research grant from CareFirst BlueCross BlueShield.

Future research on new models of care in primary care settings should assess patient experience, provider perspectives as well as implementation time, resources, and outcomes.

About George Mason University

George Mason University is Virginia's largest and most diverse public research university. Located near Washington, D.C., Mason enrolls 38,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity and commitment to accessibility. For more information, visit https://www2.gmu.edu/.

About the College of Health and Human Services

George Mason University's College of Health and Human Services prepares students to become leaders and shape the public's health through academic excellence, research of consequence and interprofessional practice. The College enrolls 1,917 undergraduate students and 950 graduate students in its nationally recognized offerings, including: 5 undergraduate degrees, 12 graduate degrees, and 11 certificate programs. The College is transitioning to a college public health in the near future. For more information, visit https://chhs.gmu.edu/.

Journal

Population Health Management

DOI

10.1089/pop.2019.0189