TRACS set the stage in flatworm regeneration

Transient regeneration-activated cell states can exist in tissues near to and distant from a wound site during planarian whole-body regeneration

Peer-Reviewed Publication

STOWERS INSTITUTE FOR MEDICAL RESEARCH

 

IMAGE: AN “ATLAS” REPRESENTATION CAPTURES THE CELLULAR COMPLEXITY OF FLATWORM REGENERATION. INDIVIDUAL FLATWORM CELLS ARE REPRESENTED BY DOTS, WITH COLORS CORRESPONDING TO COLLECTION TIME POINTS AND DISTANCES REPRESENTING SIMILARITY IN GENE EXPRESSION PROFILES. view more 

CREDIT: SÁNCHEZ ALVARADO LAB

KANSAS CITY, MO—People who fish and regularly use earthworms as bait may be familiar with the animal’s ability to regenerate a head or tail when cut in two. Yet while impressive, an earthworm’s regenerative capacity is child’s play compared with that of the planarian Schmidtea mediterranea. This species, a type of flatworm, can regrow an entire animal from tiny tissue fragments as minuscule as 1/279th of the animal.

How does this happen? What cell types contribute to this astounding regenerative capacity? Besides stem cells, which are obviously important, how many other cell types are important for regulating this process, and what do they do?

Recent research published September 2, 2021, in Nature Cell Biology by members of the Sánchez Alvarado Lab at the Stowers Institute for Medical Research provides some early answers to these complex questions.

“It was already known that the wound-induced epidermis and the wound-induced muscle played different roles in regeneration, but we wanted to understand the big picture,” explains lead author Blair Benham-Pyle, PhD, a postdoctoral scientist in the lab of Stowers Institute Executive Director and Chief Scientific Officer and Howard Hughes Medical Institute Investigator Alejandro Sánchez Alvarado, PhD.

“This is the first study that definitively found that all three germ layers (muscle, epidermis, and intestine) of Schmidtea mediterranea transcriptionally respond to amputation, and that both tissues near the wound site and far away from the wound site are contributing to regenerative capacity,” says Benham-Pyle.

“Regeneration was a little bit of a black box before—we knew some genes that were important, and we could look at how some genes were altered globally in response to amputation and during regeneration, but we didn’t know how individual cell types across the animal were changing their behavior or function. That’s what this experiment allowed us to characterize.”

“The dream experiment,” described Benham-Pyle, and what they ultimately accomplished, was to “characterize gene expression on the single-cell level, across all of the different cell types of a regenerating animal, over time.”

At first, the researchers considered doing the experiment using large-scale RNA sequencing because droplet-based single-cell sequencing—where every single cell is encapsulated in a lipid droplet with a barcode, and then lysed to label all mRNAs with that barcode— was not feasible at the scale needed for this experiment. But in early 2017, Sánchez Alvarado came across a preprint that had just been posted to bioRxiv reporting a new single-cell sequencing method named SplitSeq. Once Benham-Pyle had reviewed and discussed with Sánchez Alvarado the merits of the work in the preprint, they decided to give it a go. After several tries, a number of optimizations, and troubleshooting with the molecular biology and cytometry technology center teams, Benham-Pyle succeeded in bringing a new single-cell sequencing technology to the Stowers Institute.

After getting it to work, Benham-Pyle and colleagues captured almost 300,000 single cell transcriptomes across eight different tissues and the stem cell compartment in animals that had lost the ability to regenerate, compared with those that were capable of regenerating.

“This allowed us to look at all of the different cell types across the entire animal to see which responded to amputation and what genes were marking these cells as they changed and responded to regeneration,” explains Benham-Pyle.

The researchers found and characterized five different cell types, from all three germ layers, that transiently altered their transcriptional output after amputation. When genes enriched in these cell types were knocked down, says Benham-Pyle, “we found that all of them contribute to regeneration in different ways, being activated at different times and in different parts of the body.”

Some of their findings were more unexpected than others. For example, that muscle is important for patterning, and that the epidermis is important for early stem cell proliferation bursts during regeneration, was not as unexpected. The researchers were surprised, however, to discover rare cells, states induced during whole-body regeneration, called transient regeneration-activating cell states (TRACS), and to find that the intestine seems to be important for both stem cell maintenance and regulating tissue remodeling after amputation.

“I didn’t expect the intestine to globally change its output and remodel its function after injury,” says Benham-Pyle. “But if you think about it, it does make sense. The planarian normally grows its body plan based on its nutrient environment. The worm eats, and that fuels a burst of stem cell proliferation and the addition of new biomass. When you cut the animal, especially in extreme injury, it often loses its ability to eat. All of the growth and remodeling now needs to be fueled by nutrients already existing within the body plan. So, after amputation, the intestine alters its function to scavenge material from dying cells within the animal, and to convert those materials into new healthy cells in a regenerated worm.”

Acquiring and making sense of the data was a team effort.

“We had to do all of our manuscript revisions during the COVID-19 pandemic, when we were at 50% research capacity,” recounts Benham-Pyle. “Sean McKinney and the Microscopy Center found ways to automate imaging, and we worked out a system where I could give them forty to eighty slides at a time, of all different samples and RNAi conditions, to be imaged on overnight runs. They were able to generate terabytes of imaging data for us on the scanning confocal microscope, which helped give us the big lift we needed to get the paper accepted. They set a very high bar for microscopy facilities.”

Other coauthors of the study include: Carolyn E. Brewster, a bioinformatics specialist who helped analyze the data generated from the experiment, and was instrumental in creating the website associated with the paper; Aubrey M. Kent, who helped describe some of the first RNAi phenotypes that came out of the dataset (she is now following up on some of the epidermal genes that were found to affect the stem cell compartment); Frederick G. Mann, PhD, who helped clone many of the genes that Benham-Pyle screened and characterized in the paper; Shiyuan Chen; Allison R. Scott; and Andrew C. Box; and Alejandro Sánchez Alvarado, PhD.

Taking a step back, “what this paper does is take a global look at what sorts of cells need to be in a signaling environment to stimulate stem cells to create new tissue and replace missing tissue,” Benham-Pyle reflects.

“It turns out that a number of genes that we characterized, for instance in the intestine, have also been implicated in immune evasion in the context of cancer, or in wound healing. A lot of the same mechanisms that stem cells use to avoid the immune system and to fuel proliferation and growth during regeneration may be the same mechanisms that are co-opted by tumors. By understanding what non-stem cell states and tissue types are helping to create that signaling environment, we might eventually find new targets for either stimulating healthy and normal wound healing in contexts where regenerative capacity is limited, or, limiting growth capacities of things that we don’t want to grow, like tumors.”

“Now that we have a map, we can go and figure out how the cells are talking to each other, what they’re doing, and how they’re doing it.”

The work was supported in part by the Stowers Institute for Medical Research, the Howard Hughes Medical Institute, the National Institute of General Medical Sciences of the National Institutes of Health (award R37GM057260 to A.S.A), the Jane Coffin Childs Memorial Fund Postdoctoral Fellowship (B.W.B.P), and a Howard Hughes Medical Institute Postdoctoral Fellowship (F.G.M). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Lay Summary of Findings

The free-living planarian Schmidtea mediterranea (a type of flatworm) is capable of regenerating an entire body from a tiny portion of tissue. How it accomplishes this has largely been a mystery. In a report published September 2, 2021, in Nature Cell Biology, members from the lab of Alejandro Sánchez Alvarado, PhD, of the Stowers Institute for Medical Research, describe an atlas of cell identity and cellular behavior over time in worms that are healthy, beginning the process of regeneration, and completing regeneration.

The study, led by Blair Benham-Pyle, PhD, is the first to definitively show that whole-body regeneration involves transcriptional changes in cells from all three germ layers (muscle, epidermis, and intestine) of the body, and that tissue from areas distant from, as well as nearby to the site of injury, contribute to the process of regeneration.

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About the Stowers Institute for Medical Research 

Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit, biomedical research organization with a focus on foundational research. Its mission is to expand our understanding of the secrets of life and improve life’s quality through innovative approaches to the causes, treatment, and prevention of diseases.

The Institute consists of sixteen independent research programs. Of the approximately 500 members, over 370 are scientific staff that includes principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool.

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JOURNAL

Nature Cell Biology

ARTICLE TITLE

'Identification of rare, transient post-mitotic cell states that are induced by injury and required for whole-body regeneration in Schmidtea mediterranea

ARTICLE PUBLICATION DATE

2-Sep-2021

 

Many of the fastest-evolving human genes linked to evolutionary changes in brain development

Peer-Reviewed Publication

CELL PRESS

 

IMAGE: THIS IMAGE SHOWS A THIN SECTION TAKEN FROM THE CEREBELLUM OF AN ADULT FERRET BRAIN, WITH ASTROCYTES LABELED IN YELLOW, AND CELL NUCLEI LABELED IN BLUE. ASTROCYTES ARE A VISUALLY STRIKING TYPE OF NON-NEURAL CELL IN THE BRAIN THAT WERE FOUND TO CONTINUE TO EXPRESS PPP1R17 ONLY IN ADULT NON-HUMAN PRIMATES IN THIS STUDY, BUT NOT IN THE CEREBRAL CORTEX OR THE CEREBELLUM OF NON-PRIMATE SPECIES SUCH AS THE FERRET, SHOWN HERE. view more 

CREDIT: ELLEN DEGENNARO

More than 3,000 regions in the human genome are very different in people from in any other mammals, including our closest primate relatives. Now, a study reported in the journal Neuron on September 2 has evidence to confirm that nearly half of these so-called human accelerated regions (HARs) have played an important role in rewriting the course of human brain development, offering important insight into the genetic basis of human evolution.

“Probably one of the most interesting questions in neuroscience is, ‘What makes us human?’” says Christopher Walsh (@chrisawalsh1) of Harvard University and the Allen Discovery Center for Human Brain Evolution. “Specifically, what is it about the human brain that differentiates it from those of other closely related species? Looking at human accelerated regions provided us with a very targeted way to investigate that question from a genetic perspective.”

To systematically identify which of the 3,171 previously identified HARs are most likely to be contributing to recent evolution of the human cerebral cortex, the researchers examined the role of these regions in regulating genes in studies of multiple human and mouse cell types and tissues.

“We knew going into this study that many HARs were likely to function as regulators of gene expression in the brain, but we knew very little about which cell types in the brain they worked in, where, or at what time in the human lifespan,” explains Ellen DeGennaro (@ViolinPlots), one of the study’s first authors in the Walsh lab. “Our goal was to fill in these gaps of knowledge about which HARs had important roles in the brain, and how, so that we and other researchers could take the most important ‘brain HARs’ and perform deeper tests of their evolutionary function.”

To overcome the limitations of earlier methods, Walsh and his colleagues developed an applied approach called CaptureMPRA. The new method leverages barcoded molecular inversion probes to capture target sequences that capture entire HAR elements and their surrounding DNA, overcoming some limitations of prior techniques. Using this approach, they looked for important differences in HAR enhancer function between humans and chimpanzees.

They also integrated this data with epigenetic data at HARs in human fetal neural cells to identify HARs that looked likely to have an important role in guiding human-specific brain development. Some of the activity they uncovered was specific to the brain, as compared to other organs in the body. They also found activity that was even more specific to certain cell types in the fetal brain, as opposed to brains of adults.

CAPTION

This image shows a thin section of ferret cerebellum, with astrocytes (yellow) and cells expressing PPP1R17 (blue).

CREDIT

Ellen DeGennaro

Overall, the new findings show that many HARs do indeed appear to act as neurodevelopmental enhancers, the researchers report. The new data suggests that, as those human sequences diverged from other mammals, they have largely increased their role as neuronal enhancers.

The researchers also show that one HAR-regulated gene in particular, called PPP1R17, has undergone rapid change in both cell-type and developmental expression patterns between non-primates and primates and between non-human primates and humans. They went on to show that PPP1R17 slows the progression of neural progenitor cells through the cell cycle. This is notable given that lengthening of the cell cycle in non-human primates and humans is known to force a slowing of neurological development, an important feature of the human brain.

The new findings define many HARs that play key roles in neuronal gene regulatory programs; nearly half of all HARs show reproducible chromatin accessibility and enhancer activity in neural cells and tissue, according to the researchers. They’ve also developed an easily searchable online resource (the HARHub) consisting of the new data and previously published datasets of common and rare human HAR sequence variation. This databank now serves as a resource for scientists to make even more discoveries. Already, it has offered intriguing insights.

“Our work provides an important advance in studying many genomic regions at once to help us piece together the very complicated but compelling picture of human brain evolution,” Walsh says. “Our data suggest that evolution of the human brain involved changes in dozens or perhaps even hundreds of sites in the genome, rather than just a single key gene.”

CAPTION

This image shows a thin section of mouse cerebellum, with PP1R17-expressing cells labeled in green.

CREDIT

Ellen DeGennaro

This work was supported by the National Institutes of Health; the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation; a Career Award for Medical Scientists from the Burroughs Wellcome Fund; the Surpina and Panos Eurnekian BioFund fellowship; the Simons Foundation Autism Research Initiative Bridge to Independence award; and the Simons Center for the Social Brain postdoctoral fellowship. C.A.W. is an Investigator of the Howard Hughes Medical Institute.

Neuron, Girskis et al.: “Rewiring of human neurodevelopmental gene regulatory programs by Human Accelerated Regions (HARs)” https://www.cell.com/neuron/fulltext/S0896-6273(21)00580-8

Neuron (@NeuroCellPress), published by Cell Press, is a bimonthly journal that has established itself as one of the most influential and relied upon journals in the field of neuroscience and one of the premier intellectual forums of the neuroscience community. It publishes interdisciplinary articles that integrate biophysical, cellular, developmental, and molecular approaches with a systems approach to sensory, motor, and higher-order cognitive functions. Visit: http://www.cell.com/neuron. To receive Cell Press media alerts, contact press@cell.com.

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JOURNAL

Neuron

DOI

10.1016/j.neuron.2021.08.005 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Human tissue samples

ARTICLE TITLE

Rewiring of human neurodevelopmental gene regulatory programs by Human Accelerated Regions (HARs)

ARTICLE PUBLICATION DATE

2-Sep-2021

 

Scientists create a labor-saving automated method for studying electronic health records

Mount Sinai study suggests new method is as effective as manually-based “gold-standard” at classifying a diagnosis

Peer-Reviewed Publication

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

 

IMAGE: MOUNT SINAI SCIENTISTS CREATED AN AI-BASED, AUTOMATED SYSTEM THAT LEARNS TO READ PATIENT DATA FROM ELECTRONIC HEALTH RECORDS. HERE THE SYSTEM IDENTIFIED DEMENTIA CASES (PURPLE DOTS) FROM A DATABASE OF NEARLY 2 MILLION PATIENTS (BLUE DOTS). view more 

CREDIT: COURTESY OF THE GLICKSBERG LAB, MOUNT SINAI, N.Y., N.Y.

In an article published in the journal Patterns, scientists at the Icahn School of Medicine at Mount Sinai described the creation of a new, automated, artificial intelligence-based algorithm that can learn to read patient data from electronic health records. In a side-by-side comparison, they showed that their method, called Phe2vec (FEE-to-vek), accurately identified patients with certain diseases as well as the traditional, “gold-standard” method, which requires much more manual labor to develop and perform.

“There continues to be an explosion in the amount and types of data electronically stored in a patient’s medical record. Disentangling this complex web of data can be highly burdensome, thus slowing advancements in clinical research,” said Benjamin S. Glicksberg, PhD, Assistant Professor of Genetics and Genomic Sciences, a member of the Hasso Plattner Institute for Digital Health at Mount Sinai (HPIMS), and a senior author of the study. “In this study, we created a new method for mining data from electronic health records with machine learning that is faster and less labor intensive than the industry standard. We hope that this will be a valuable tool that will facilitate further, and less biased, research in clinical informatics.”

The study was led by Jessica K. De Freitas, a graduate student in Dr. Glicksberg lab.

Currently, scientists rely on a set of established computer programs, or algorithms, to mine medical records for new information. The development and storage of these algorithms is managed by a system called the Phenotype Knowledgebase (PheKB). Although the system is highly effective at correctly identifying a patient diagnosis, the process of developing an algorithm can be very time-consuming and inflexible. To study a disease, researchers first have to comb through reams of medical records looking for pieces of data, such as certain lab tests or prescriptions, which are uniquely associated with the disease. They then program the algorithm that guides the computer to search for patients who have those disease-specific pieces of data, which constitute a “phenotype”. In turn, the list of patients identified by the computer needs to be manually double-checked by researchers. Each time researchers want to study a new disease, they have to restart the process from scratch.

In this study, the researchers tried a different approach—one in which the computer learns, on its own, how to spot disease phenotypes and thus save researchers time and effort. This new, Phe2vec method was based on studies the team had already conducted.

“Previously, we showed that unsupervised machine learning could be a highly efficient and effective strategy for mining electronic health records,” said Riccardo Miotto, PhD, a former Assistant Professor at the HPIMS and a senior author of the study. “The potential advantage of our approach is that it learns representations of diseases from the data itself. Therefore, the machine does much of the work experts would normally do to define the combination of data elements from health records that best describes a particular disease.”

Essentially, a computer was programmed to scour through millions of electronic health records and learn how to find connections between data and diseases. This programming relied on “embedding” algorithms that had been previously developed by other researchers, such as linguists, to study word networks in various languages. One of the algorithms, called word2vec, was particularly effective. Then, the computer was programmed to use what it learned to identify the diagnoses of nearly 2 million patients whose data was stored in the Mount Sinai Health System.

Finally, the researchers compared the effectiveness between the new and the old systems. For nine out of ten diseases tested, they found that the new Phe2vec system was as effective as, or performed slightly better than, the gold standard phenotyping process at correctly identifying a diagnoses from electronic health records. A few examples of the diseases included dementia, multiple sclerosis, and sickle cell anemia.

“Overall our results are encouraging and suggest that Phe2vec is a promising technique for large-scale phenotyping of diseases in electronic health record data,” Dr. Glicksberg said. “With further testing and refinement, we hope that it could be used to automate many of the initial steps of clinical informatics research, thus allowing scientists to focus their efforts on downstream analyses like predictive modeling.”

This study was supported by the Hasso Plattner Foundation, the Alzheimer’s Drug

Discovery Foundation, and a courtesy graphics processing unit donation from the NVIDIA Corporation.

Article

De Freitas, J.K., et al., Phe2vec: Automated Disease Phenotyping based on Unsupervised Embeddings from Electronic Health Records, Patterns, September 2, 2021, DOI: 10.1016/j.patter.2021.100337.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

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JOURNAL

Patterns

DOI

10.1016/j.patter.2021.100337 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Phe2vec: Automated Disease Phenotyping based on Unsupervised Embeddings from Electronic Health Records

ARTICLE PUBLICATION DATE

2-Sep-2021

 

Nano ‘camera’ made using molecular glue allows real-time monitoring of chemical reactions

Peer-Reviewed Publication

UNIVERSITY OF CAMBRIDGE

 

IMAGE: THE DEVICE, MADE BY A TEAM FROM THE UNIVERSITY OF CAMBRIDGE, COMBINES TINY SEMICONDUCTOR NANOCRYSTALS CALLED QUANTUM DOTS AND GOLD NANOPARTICLES USING MOLECULAR GLUE CALLED CUCURBITURIL (CB). WHEN ADDED TO WATER WITH THE MOLECULE TO BE STUDIED, THE COMPONENTS SELF-ASSEMBLE IN SECONDS INTO A STABLE, POWERFUL TOOL THAT ALLOWS THE REAL-TIME MONITORING OF CHEMICAL REACTIONS. view more 

CREDIT: UNIVERSITY OF CAMBRIDGE

Researchers have made a tiny camera, held together with ‘molecular glue’ that allows them to observe chemical reactions in real time.

The device, made by a team from the University of Cambridge, combines tiny semiconductor nanocrystals called quantum dots and gold nanoparticles using molecular glue called cucurbituril (CB). When added to water with the molecule to be studied, the components self-assemble in seconds into a stable, powerful tool that allows the real-time monitoring of chemical reactions.

The camera harvests light within the semiconductors, inducing electron transfer processes like those that occur in photosynthesis, which can be monitored using incorporated gold nanoparticle sensors and spectroscopic techniques. They were able to use the camera to observe chemical species which had been previously theorised but not directly observed.

The platform could be used to study a wide range of molecules for a variety of potential applications, such as the improvement of photocatalysis and photovoltaics for renewable energy. The results are reported in the journal Nature Nanotechnology.

Nature controls the assemblies of complex structures at the molecular scale through self-limiting processes. However, mimicking these processes in the lab is usually time-consuming, expensive and reliant on complex procedures.

“In order to develop new materials with superior properties, we often combine different chemical species together to come up with a hybrid material that has the properties we want,” said Professor Oren Scherman from Cambridge’s Yusuf Hamied Department of Chemistry, who led the research. “But making these hybrid nanostructures is difficult, and you often end up with uncontrolled growth or materials that are unstable.”

The new method that Scherman and his colleagues from Cambridge’s Cavendish Laboratory and University College London developed uses cucurbituril – a molecular glue which interacts strongly with both semiconductor quantum dots and gold nanoparticles. The researchers used small semiconductor nanocrystals to control the assembly of larger nanoparticles through a process they coined interfacial self-limiting aggregation. The process leads to permeable and stable hybrid materials that interact with light. The camera was used to observe photocatalysis and track light-induced electron transfer.

“We were surprised how powerful this new tool is, considering how straightforward it is to assemble,” said first author Dr Kamil Sokołowski, also from the Department of Chemistry.

To make their nano camera, the team added the individual components, along with the molecule they wanted to observe, to water at room temperature. Previously, when gold nanoparticles were mixed with the molecular glue in the absence of quantum dots, the components underwent unlimited aggregation and fell out of solution. However, with the strategy developed by the researchers, quantum dots mediate the assembly of these nanostructures so that the semiconductor-metal hybrids control and limit their own size and shape. In addition, these structures stay stable for weeks.

“This self-limiting property was surprising, it wasn’t anything we expected to see,” said co-author Dr Jade McCune, also from the Department of Chemistry. “We found that the aggregation of one nanoparticulate component could be controlled through the addition of another nanoparticle component.”

When the researchers mixed the components together, the team used spectroscopy to observe chemical reactions in real time. Using the camera, they were able to observe the formation of radical species – a molecule with an unpaired electron – and products of their assembly such as sigma dimeric viologen species, where two radicals form a reversible carbon-carbon bond. The latter species had been theorised but never observed.

“People have spent their whole careers getting pieces of matter to come together in a controlled way,” said Scherman, who is also Director of the Melville Laboratory. “This platform will unlock a wide range of processes, including many materials and chemistries that are important for sustainable technologies. The full potential of semiconductor and plasmonic nanocrystals can now be explored, providing an opportunity to simultaneously induce and observe photochemical reactions.”

“This platform is a really big toolbox considering the number of metal and semiconductor building blocks that can be now coupled together using this chemistry– it opens up lots of new possibilities for imaging chemical reactions and sensing through taking snapshots of monitored chemical systems,” said Sokołowski. “The simplicity of the setup means that researchers no longer need complex, expensive methods to get the same results.”

Researchers from the Scherman lab are currently working to further develop these hybrids towards artificial photosynthetic systems and (photo)catalysis where electron-transfer processes can be observed directly in real time. The team is also looking at mechanisms of carbon-carbon bond formation as well as electrode interfaces for battery applications.

The research was carried out in collaboration with Professor Jeremy Baumberg at Cambridge’s Cavendish Laboratory and Dr Edina Rosta at University College London. It was funded in part by the Engineering and Physical Sciences Research Council (EPSRC).

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JOURNAL

Nature Nanotechnology

DOI

10.1038/s41565-021-00949-6 

METHOD OF RESEARCH

Experimental study

ARTICLE TITLE

Nanoparticle surfactants for kinetically arrested photoactive assemblies to track light-induced electron transfer

ARTICLE PUBLICATION DATE

1-Sep-2021

 

Researchers sequence genome of drug-resistant Salmonella enteritidis strain that can sicken poultry

Peer-Reviewed Publication

NORTH CAROLINA STATE UNIVERSITY

Researchers from North Carolina State University sequenced the genome of a virulent Salmonella Enteritidis strain that sickened two poultry flocks in consecutive years and found that it was both antibiotic resistant and could potentially infect humans. Characterizing the strain, designated SE_TAU19, will aid public health agencies in tracing outbreaks and preventing exposures.

There are two species of Salmonella, and one of these, Salmonella enterica, is implicated in human disease. S. enterica contains over 2,500 serovars, or groups of bacteria, many of which can cause disease in humans. Salmonella serovar Enteritidis (SE) is most frequently associated with poultry and is the leading cause of human illness globally.

Most human Salmonella infections are foodborne in origin, and many animals – such as chickens – can harbor the pathogen without becoming sick themselves. The ability of SE_TAU19 to cause clinical disease in poultry interested Grayson Walker, a combined DVM and Ph.D. student in Luke Borst’s laboratory at NC State’s College of Veterinary Medicine and first author of a paper describing the research.

“We usually think of Salmonella as harbored by chickens without harming them; however, this strain was virulent and actually made them sick,” Walker says. “We also know that Salmonella likes to stick around. This strain killed broiler chickens throughout the growing period and recurred one year later in a different flock. So, we decided to sequence the genome and see which resistance and virulence features made the strain unique.”

The team sequenced the genome of the strain and found that it included seven antimicrobial resistance genes, 120 virulence genes, and a large virulence plasmid. Plasmids are “swappable” genetic elements that can be exchanged between strains to make them more antibiotic resistant or infectious.

“While we cannot say that it is a ‘new’ strain of Salmonella, we can say that not only is this strain deadly to poultry, antibiotic resistant and infectious, but also that it could infect humans,” Walker says. “The good news is that by sequencing the genome we now have data that could help pinpoint the origin of and contain any future outbreaks.”

The research appears in Frontiers in Veterinary Science and is supported by the United States Department of Agriculture Animal Plant Health Inspection Service’s National Bio and Agro-defense Facility Scientist Training Program. Whole-genome sequencing was completed by the FDA GenomeTrakr program funded under grant 1U18FD00678801 in the lab of co-author Sid Thakur, professor of population health and pathobiology and the director of NC State’s and the College of Veterinary Medicine’s Global Health programs. Borst, associate professor of veterinary anatomic pathology at NC State, is corresponding author.

-peake-

Note to editors: An abstract follows.

“Genomic characterization of a nalidixic acid-resistant Salmonella Enteritidis strain causing persistent infections in broiler chickens”

DOI: 10.3389/fvets.2021.725737

Authors: Grayson K. Walker, M. Mitsu Suyemoto, Dawn M. Hull, Sesny Gall, Fernando Jimenez, Laura R. Chen, Siddhartha Thakur, Rocio Crespo, and Luke B. Borst, North Carolina State University

Published: Sept. 1, 2021 in Frontiers in Veterinary Science

Abstract:
Virulent strains of Salmonella enterica subsp. enterica serovar Enteritidis (SE) harbored by poultry can cause disease in poultry flocks and potentially result in human foodborne illness. Two broiler flocks grown a year apart on the same premises experienced mortality throughout the growing period due to septicemic disease caused by SE. Gross lesions predominantly consisted of polyserositis followed by yolk sacculitis, arthritis, osteomyelitis, and spondylitis. Tissues with lesions were cultured yielding 59 SE isolates. These were genotyped by Rep-PCR followed by whole-genome sequencing of 15 isolates which were clonal. The strain, SE_TAU19, was further characterized for antimicrobial susceptibility and virulence in a broiler embryo lethality assay. SE_TAU19 was resistant to nalidixic acid and sulfadimethoxine and was virulent to embryos with 100% mortality of all challenged broiler embryos within 3.5 d. Screening the SE_TAU19 whole-genome sequence revealed 7 antimicrobial resistance genes, 120 virulence genes, and 2 IncF plasmid replicons corresponding to a single, serovar-specific pSEV virulence plasmid. The pef, spv, and rck virulence genes localized to the plasmid sequence assembly. We report phenotypic and genomic features of a virulent SE strain from persistently infected broiler flocks and present a workflow for SE characterization from isolate collection to genome assembly and sequence analysis. Further SE surveillance and investigation of SE virulence in broiler chickens is warranted.

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JOURNAL

Frontiers in Veterinary Science

DOI

10.3389/fvets.2021.725737 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Genomic characterization of a nalidixic acid-resistant Salmonella Enteritidis strain causing persistent infections in broiler chickens

ARTICLE PUBLICATION DATE

1-Sep-2021

 

Study: Normal concussion recovery could take up to a month

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

Video

The largest study of concussion ever conducted in college athletes is redefining the timeline for recovery as a process taking up to 28 days, up from the suggested normal recovery time of up to 14 days. 

The findings are detailed in the journal Sports Medicine, in one of the marquee papers to emerge from the NCAA-DoD Concussion Assessment, Research and Education Consortium. The study's lead researcher, Steve Broglio, director of the University of Michigan Concussion Center, is on the CARE Consortium leadership team and leads the CARE clinical study core. 

"Normal return-to-play time was previously set at 14 days––meaning 50% of people recovered in that time. Our paper suggests that 28 days more fully encapsulates the recovery process. At that point, 85% of people have returned to play," Broglio said.

The study found that though median recovery times were consistent with the previously suggested 14 days, it was not until one month post-injury that most athletes were cleared for unrestricted sport participation. 

This doesn't mean that universities must revise their return to play protocols.  

"The RTP protocols are driven by clinical presentation (symptoms), not time, so they don't need to be revised," Broglio said.  

Rather, coaches, parents and athletes should reframe their expectations for return to

play, in part to avoid stigmatizing concussed athletes who take longer than 14 days to recover, he said. Reframing the normal recovery time to 28 days helps eliminate unintentional social pressure from teammates, coaches or parents who hope to see their player back on the field. If a concussed athlete takes longer than 14 days or up to a month, that's completely normal, he said.

There wasn't much variation in recovery times among study subgroups, with various factors altering recovery by only up to two days. The total return-to-play duration was shorter with ADHD medication usage, males and greater assessment frequency. Those with greater initial post-injury symptom severity, practice/training-related injuries and three or more prior concussions had longer recoveries. 

Concussion management recommendations are outlined every four years by the Concussion in Sport Group, an international body that reviews the medical literature and develops guidelines on clinical care. This paper and others resulting from the CARE Consortium will likely be taken into consideration when the group meets next year, said Broglio, who is also a member of CISG.

Despite increased research in concussion over the previous decade, the trajectory of concussion recovery times across diverse populations of athletes has remained poorly defined, because most sport concussion research centered on male athletes in collision sports, or on female soccer players, Broglio said. 

The current study included 34,709 male and female athletes from 30 colleges and universities—more than 1,700 of whom were concussed while participating in 22 sports.

Concussed male athletes most commonly played football (54.7%), soccer (10.7%), basketball (6.8%) and wrestling (6.4%), while concussed female athletes most commonly played soccer (23.4%), volleyball (14%), basketball (12.9%) and lacrosse (8.4%). Broglio said male and female athletes took about the same amount of time to recover from concussion, give or take a day.

Concussion education and treatment has improved dramatically in the last two decades, he said.

"Back when I started in concussion research 20 years ago, we'd manage these

injuries with a light switch. We'd ask, 'Do you have symptoms?' and if the answer was no, the athlete was put back on the field. Gone are the days when concussed athletes are put back in the same day," Broglio said. "Now, we can think of it as a dial, where we

slowly progress people back into the sport. Once a player is asymptomatic, it can still take some time. We have to respect the injury and respect the recovery process."

Co-authors include: Thomas McAllister, Barry Katz, Michelle LaPradd and Wenxian Zhou of Indiana University; Michael McCrea of the Medical College of Wisconsin; and CARE Consortium investigators. 

Study: The Natural History of Sport-Related Concussion in Collegiate Athletes: Findings from the NCAA-DoD CARE Consortium

JOURNAL

Sports Medicine

Green Party leader accidentally endorses Liberal environment plan

Richard Raycraft 

It was an endorsement Justin Trudeau and the Liberals probably weren't expecting.

At a press conference this afternoon in Toronto, Green Party Leader Annamie Paul appeared to give a thumbs-up to the Liberals' plan on climate change.

"I'll tell the people of Canada that if you want a real plan, one that is going to grow our economy, that is going to put us at the front of the competitive green economy of the future ... the only option in this election for you is the Liberals," Paul said.

In a media statement subsequently sent to CBC News, Paul's press secretary Rosie Emery said the Green leader misspoke.

"Ms. Paul does not support the Liberal climate plan. What she meant to say was that the Green Party cannot support it, and that we must work collaboratively to confront climate change and that the Green Party platform remains the only platform with clear climate action," the statement reads.

In a video posted to Twitter, Paul acknowledged both the mistake and its potential as a meme.

"It was bound to happen. You do one press conference too many without having had your lunch, and there you go — saying things that are definitely, definitely good for a meme." Paul said in a video posted to Twitter.

"What I meant to say is that if you want real action on the climate, if you want the real possibility of the strong, green economy of the future, if you want Canada to join the green rush that's going on globally, then there's one option and one option only, and that is ... the Greens."

WHILE IN MANITOBA NDP LEADER JAGMEET SINGH WAS ACCOMPANIED BY FIRST NATIONS LEADERS AT ONE RIDING WHERE THEY ANNOUNCED THEIR  SUPPORT FOR THE LIBERAL OPPOSING THE NDP INCUMBENT MP