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Mussel sensors pave the way for new environmental monitoring tools




Researchers at North Carolina State University have designed and demonstrated a new system that allows them to remotely monitor the behavior of freshwater mussels. The system could be used to alert researchers to the presence of toxic substances in aquatic ecosystems.

“When mussels feed, they open their shells; but if there’s something noxious in the water, they may immediately close their shells, all at once,” says Jay Levine, co-author of a paper on the work and a professor of epidemiology at NC State. “Folks have been trying to find ways to measure how widely mussels or oysters open their shells off and on since the 1950s, but there have been a wide variety of challenges. We needed something that allows the animals to move, can be placed in streams and collects data – and now we have it.”

“We’ve basically designed a custom Fitbit to track the activities of mussels,” says Alper Bozkurt, corresponding author of the paper and a professor of electrical and computer engineering at NC State.

The fundamental idea for the research stems from the fact that feeding behavior in mussels is generally asynchronous – it’s not a coordinated affair. So, if a bunch of mussels close their shells at once, that’s likely a warning there’s something harmful in the water.

One of the things the researchers are already doing with the new sensor system is monitoring mussel behavior to determine if there are harmless circumstances in which mussels may all close their shells at the same time.

“Think of it as a canary in the coal mine, except we can detect the presence of toxins without having to wait for the mussels to die,” Levine says. “At the same time, it will help us understand the behavior and monitor the health of the mussels themselves, which could give us insights into how various environmental factors affect their health. Which is important, given that many freshwater mussel species are threatened or endangered.”

“To minimize costs, all the components we used to make this prototype sensor system are commercially available – we’re just using the technologies in a way nobody has used them before,” Bozkurt says.

Specifically, the system uses two inertial measurement units (IMUs) on each mussel. Each of the IMUs includes a magnetometer and an accelerometer – like the ones used in smartphones to detect when you are moving the phone. One IMU is attached to the mussel’s top shell, the other to its bottom shell. This allows the researchers to compare the movement of the shell halves relative to each other. In other words, this allows the researchers to tell if the mussel is closing its shell, as opposed to the mussel being tumbled in the water by a strong current.

Wires from the IMUs are designed to run to a data acquisition system that would be mounted on a stake in the waterway. When placed in a natural setting, the data acquisition system is powered by a solar cell and transmits data from the sensors wirelessly via a cellular network. The current prototype has four mussels connected to the system, but it could handle dozens.

The researchers did more than 250 hours of testing with live mussels in a laboratory fish tank, and found that the sensors were exceptionally accurate – measuring the angle of the mussel’s shell opening to within less than one degree.

“You can definitely tell when it’s closed, when it’s open and by how much,” Bozkurt says.

“Our aim is to establish an ‘internet-of-mussels’ and monitor their individual and collective behavior,” Bozkurt says. “This will ultimately enable us to use them as environmental sensors or sentinels.”

The researchers are now continuing their testing to better understand the robustness of the system. For example, how long might it last in practical use under real-life conditions? The team plans to begin field testing soon.

“In addition to exploring its effectiveness as an environmental monitor, we’re optimistic that the technology can help us learn new things about the mussels themselves,” Levine says. “What prompts them to filter and feed? Does their behavior change in response to changes in temperature? While we know a lot about these animals, there is also a lot we don’t know. The sensors provide us with the opportunity to develop baseline values for individual animals, and to monitor their shell movement in response to environmental changes.”


The paper, “An Accelerometer-Based Sensing System to Study the Valve-Gaping Behavior of Bivalves,” is published in the journal IEEE Sensors Letters. Parvez Ahmmed and James Reynolds were co-lead authors on the paper. Both are Ph.D. students at NC State and were co-mentored by Bozkurt and Levine.

The work was done with support from the National Science Foundation, under grants 1160483 and 1554367; and from the U.S. Fish and Wildlife Service, under grant 2018-0535/F18AC00237.

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COVID-19 vaccine does not damage the placenta in pregnancy




CHICAGO — A new Northwestern Medicine study of placentas from patients who received the COVID-19 vaccine during pregnancy found no evidence of injury, adding to the growing literature that COVID-19 vaccines are safe in pregnancy.

“The placenta is like the black box in an airplane. If something goes wrong with a pregnancy, we usually see changes in the placenta that can help us figure out what happened,” said corresponding author Dr. Jeffery Goldstein, assistant professor of pathology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine pathologist. “From what we can tell, the COVID vaccine does not damage the placenta.”

The study will be published May 11 in the journal Obstetrics & Gynecology. To the authors’ knowledge, it is the first study to examine the impact of the COVID vaccines on the placenta.

“We have reached a stage in vaccine distribution where we are seeing vaccine hesitancy, and this hesitancy is pronounced for pregnant people,” said study co-author Dr. Emily Miller, Northwestern Medicine maternal fetal medicine physician and assistant professor of obstetrics and gynecology at Feinberg. “Our team hopes these data, albeit preliminary, can reduce concerns about the risk of the vaccine to the pregnancy.”

The study authors collected placentas from 84 vaccinated patients and 116 unvaccinated patients who delivered at Prentice Women’s Hospital in Chicago and pathologically examined the placentas whole and microscopically following birth. Most patients received vaccines – either Moderna or Pfizer – during their third trimester.

Last May, Goldstein, Miller and collaborators from Northwestern and Ann & Robert H. Lurie Children’s Hospital of Chicago published a study that found placentas of women who tested positive for the COVID-19 virus while pregnant showed evidence of injury (abnormal blood flow between mother and baby in utero). Pregnant patients who want to get vaccinated to avoid contracting the disease should feel safe doing so, Miller said.

“We are beginning to move to a framework of protecting fetuses through vaccination, rather than from vaccination,” Miller said.

In April, the scientists published a study showing pregnant women make COVID antibodies after vaccination and successfully transfer them to their fetuses.

“Until infants can get vaccinated, the only way for them to get COVID antibodies is from their mother,” Goldstein said.

The placenta’s role in the immune system

The placenta is the first organ that forms during pregnancy. It performs duties for most of the fetus’ organs while they’re still forming, such as providing oxygen while the lungs develop and nutrition while the gut is forming.

Additionally, the placenta manages hormones and the immune system, and tells the mother’s body to welcome and nurture the fetus rather than reject it as a foreign intruder.

“The Internet has amplified a concern that the vaccine might trigger an immunological response that causes the mother to reject the fetus,” Goldstein said. “But these findings lead us to believe that doesn’t happen.”

The scientists also looked for abnormal blood flow between the mother and fetus and problems with fetal blood flow – both of which have been reported in pregnant patients who have tested positive for COVID.

The rate of these injuries was the same in the vaccinated patients as for control patients, Goldstein said. The scientists also examined the placentas for chronic histiocytic intervillositis, a complication that can happen if the placenta is infected, in this case, by SARS-CoV-2. Although this study did not find any cases in vaccinated patients, it’s a very rare condition that requires a larger sample size (1,000 patients) to differentiate between vaccinated and unvaccinated patients.


Other Northwestern study authors include Dr. Elisheva Shanes and Chiedza Mupanomunda. Dr. Leena B. Mithal and Sebastian Otero from Lurie Children’s Hospital also are study authors.

The study was funded by The Friends of Prentice, the Stanley Manne Children’s Research Institute, the National Institute of Biomedical Imaging and Bioengineering (grant number K08EB030120) and the National Institute of Allergy and Infectious Diseases (grant number K23AI139337), part of the National Institutes of Health.

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History of giants in the gene: Scientists use DNA to trace the origins of giant viruses




Scientists investigate the evolution of Mimivirus, one of the world’s largest viruses, through how they replicate DNA

2003 was a big year for virologists. The first giant virus was discovered in this year, which shook the virology scene, revising what was thought to be an established understanding of this elusive group and expanding the virus world from simple, small agents to forms that are as complex as some bacteria. Because of their link to disease and the difficulties in defining them–they are biological entities but do not fit comfortably in the existing tree of life–viruses incite the curiosity of many people.

Scientists have long been interested in how viruses evolved, especially when it comes to giant viruses that can produce new viruses with very little help from the host–in contrast to most small viruses, which utilize the host’s machinery to replicate.

Even though giant viruses are not what most people would think of when it comes to viruses, they are actually very common in oceans and other water bodies. They infect single-celled aquatic organisms and have major effects on the latter’s population. In fact, Dr. Kiran Kondabagil, molecular virologist at the Indian Institute of Technology (IIT) Bombay, suggests, “Because these single-celled organisms greatly influence the carbon turnover in the ocean, the viruses have an important role in our world’s ecology. So, it is just as important to study them and their evolution, as it is to study the disease-causing viruses.”

In a recent study, the findings of which have been published in Molecular Biology and Evolution, Dr. Kondabagil and co-researcher Dr. Supriya Patil performed a series of analyses on major genes and proteins involved in the DNA replication machinery of Mimivirus, the first group of giant viruses to be identified. They aimed to determine which of two major suggestions regarding Mimivirus evolution–the reduction and the virus-first hypotheses–were more supported by their results. The reduction hypothesis suggests that the giant viruses emerged from unicellular organisms and shed genes over time; the virus-first hypothesis suggests that they were around before single-celled organisms and gained genes, instead.

Dr. Kondabagil and Dr. Patil created phylogenetic trees with replication proteins and found that those from Mimivirus were more closely related to eukaryotes than to bacteria or small viruses. Additionally, they used a technique called multidimensional scaling to determine how similar the Mimiviral proteins are. A greater similarity would indicate that the proteins co-evolved, which means that they are linked together in a larger protein complex with coordinated function. And indeed, their findings showed greater similarity. Finally, the researchers showed that genes related to DNA replication are similar to and fall under purifying selection, which is natural selection that removes harmful gene variants, constraining the genes and preventing their sequences from varying. Such a phenomenon typically occurs when the genes are involved in essential functions (like DNA replication) in an organism.

Taken together, these results imply that Mimiviral DNA replication machinery is ancient and evolved over a long period of time. This narrows us down to the reduction hypothesis, which suggests that the DNA replication machinery already existed in a unicellular ancestor, and the giant viruses were formed after getting rid of other structures in the ancestor, leaving only replication-related parts of the genome.

“Our findings are very exciting because they inform how life on earth has evolved,” Dr. Kondabagil says. “Because these giant viruses probably predate the diversification of the unicellular ancestor into bacteria, archaea, and eukaryotes, they should have had major influence on the subsequent evolutionary trajectory of eukaryotes, which are their hosts.”

In terms of applications beyond this contribution to basic scientific knowledge, Dr. Kondabagil feels that their work could lay the groundwork for translational research into technology like genetic engineering and nanotechnology. He says, “An increased understanding of the mechanisms by which viruses copy themselves and self-assemble means we could potentially modify these viruses to replicate genes we want or create nanobots based on how the viruses function. The possibilities are far-reaching!”



Authors: Kiran Kondabagil and Supriya Patil

Title of original paper: Coevolutionary and Phylogenetic Analysis of Mimiviral Replication Machinery Suggest the Cellular Origin of Mimiviruses

Journal: Molecular Biology and Evolution


Affiliations: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India

About Dr. Kiran Kondabagil from IIT Bombay

Dr. Kondabagil is an Associate Professor in the Department of Biosciences and Bioengineering at the Indian Institute of Technology Bombay. He is also the Principal Investigator of the Molecular Virology Lab in the department. He has been a Post-doctoral Fellow and Assistant Professor at The Catholic University of America, Washington DC. He has about 9 journal articles, 3 book chapters, and 8 patents to his name. His chief areas of interest are bacteriophages, molecular microbiology, and gene targeting.

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Tiny, wireless, injectable chips use ultrasound to monitor body processes




Columbia Engineers develop the smallest single-chip system that is a complete functioning electronic circuit; implantable chips visible only in a microscope point the way to developing chips that can be injected into the body with a hypodermic needle

New York, NY–May 11, 2021–Widely used to monitor and map biological signals, to support and enhance physiological functions, and to treat diseases, implantable medical devices are transforming healthcare and improving the quality of life for millions of people. Researchers are increasingly interested in designing wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. These devices could be used to monitor physiological conditions, such as temperature, blood pressure, glucose, and respiration for both diagnostic and therapeutic procedures.

To date, conventional implanted electronics have been highly volume-inefficient–they generally require multiple chips, packaging, wires, and external transducers, and batteries are often needed for energy storage. A constant trend in electronics has been tighter integration of electronic components, often moving more and more functions onto the integrated circuit itself.

Researchers at Columbia Engineering report that they have built what they say is the world’s smallest single-chip system, consuming a total volume of less than 0.1 mm3. The system is as small as a dust mite and visible only under a microscope. In order to achieve this, the team used ultrasound to both power and communicate with the device wirelessly. The study was published online May 7 in Science Advances.

“We wanted to see how far we could push the limits on how small a functioning chip we could make,” said the study’s leader Ken Shepard, Lau Family professor of electrical engineering and professor of biomedical engineering. “This is a new idea of ‘chip as system’–this is a chip that alone, with nothing else, is a complete functioning electronic system. This should be revolutionary for developing wireless, miniaturized implantable medical devices that can sense different things, be used in clinical applications, and eventually approved for human use.”

The team also included Elisa Konofagou, Robert and Margaret Hariri Professor of Biomedical engineering and professor of radiology, as well as Stephen A. Lee, PhD student in the Konofagou lab who assisted in the animal studies.

The design was done by doctoral student Chen Shi, who is the first author of the study. Shi’s design is unique in its volumetric efficiency, the amount of function that is contained in a given amount of volume. Traditional RF communications links are not possible for a device this small because the wavelength of the electromagnetic wave is too large relative to the size of the device. Because the wavelengths for ultrasound are much smaller at a given frequency because the speed of sound is so much less than the speed of light, the team used ultrasound to both power and communicate with the device wirelessly. They fabricated the “antenna” for communicating and powering with ultrasound directly on top of the chip.

The chip, which is the entire implantable/injectable mote with no additional packaging, was fabricated at the Taiwan Semiconductor Manufacturing Company with additional process modifications performed in the Columbia Nano Initiative cleanroom and the City University of New York Advanced Science Research Center (ASRC) Nanofabrication Facility.

Shepard commented, “This is a nice example of ‘more than Moore’ technology–we introduced new materials onto standard complementary metal-oxide-semiconductor to provide new function. In this case, we added piezoelectric materials directly onto the integrated circuit to transducer acoustic energy to electrical energy.”

Konofagou added, “Ultrasound is continuing to grow in clinical importance as new tools and techniques become available. This work continues this trend.”

The team’s goal is to develop chips that can be injected into the body with a hypodermic needle and then communicate back out of the body using ultrasound, providing information about something they measure locally. The current devices measure body temperature, but there are many more possibilities the team is working on.


About the Study

The study is titled “Application of a sub-0.1-mm3 implantable mote for in vivo real-time wireless temperature sensing.”

Authors are: Chen Shi1, Victoria Andino-Pavlovsky1, Stephen A. Lee2, Tiago Costa1,3, Jeffrey Elloian1, Elisa E. Konofagou2,4, Kenneth L. Shepard1,2

1 Department of Electrical Engineering, Columbia University

2Department of Biomedical Engineering, Columbia University

3Department of Microelectronics, Delft University of Technology, The Netherlands

4Department of Radiology, Columbia University

The study was supported in part by a grant from the W. M. Keck Foundation and by the Defense Advanced Research Projects Agency (DARPA) under Contract HR0011-15-2-0054 and Cooperative Agreement D20AC00004.

Chen Shi and Kenneth L. Shepard are listed as inventors on a provisional patent filed by Columbia University (Patent Application No. 15/911,973). The other authors declare
no competing interests.



DOI: 10.1126/sciadv.abf6312

Columbia Engineering

Columbia Engineering, based in New York City, is one of the top engineering schools in the U.S. and one of the oldest in the nation. Also known as The Fu Foundation School of Engineering and Applied Science, the School expands knowledge and advances technology through the pioneering research of its more than 220 faculty, while educating undergraduate and graduate students in a collaborative environment to become leaders informed by a firm foundation in engineering. The School’s faculty are at the center of the University’s cross-disciplinary research, contributing to the Data Science Institute, Earth Institute, Zuckerman Mind Brain Behavior Institute, Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, “Columbia Engineering for Humanity,” the School aims to translate ideas into innovations that foster a sustainable, healthy, secure, connected, and creative humanity.

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Gene editing expands to new types of immune cells




Gladstone researchers fine-tuned CRISPR-Cas9 genome editing to work on human immune cells called monocytes

In the decade since the advent of CRISPR-Cas9 gene editing, researchers have used the technology to delete or change genes in a growing number of cell types. Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have added human monocytes–white blood cells that play key roles in the immune system–to that list.

The team has adapted CRISPR-Cas9 for use in monocytes and shown the potential utility of the technology for understanding how the human immune system fights viruses and microbes. Their results were published online today in the journal Cell Reports.

“These experiments set the stage for many more studies on the interactions between major infectious diseases and human immune cells,” says senior author Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and associate professor of medicine at UCSF.

“This technology opens doors for identifying the human genes most important to the function of monocytes and for coming up with new therapeutic strategies against a range of pathogens,” adds co-senior author Nevan Krogan, PhD, senior investigator at Gladstone and director of the Quantitative Biosciences Institute at UCSF.

From One Immune Cell to Another

Monocytes are immune cells with a broad range of roles in defending the human body from pathogens. As part of their normal function, monocytes can give rise to two other immune cell types: macrophages, which engulf and destroy foreign material in the body, and dendritic cells, which help recognize pathogens and trigger more specific immune responses.

Marson’s team has previously studied T cells, a different class of immune cell, using CRISPR-Cas9 technology to selectively remove genes from the cells and observe the consequences. Their results have helped point toward targets for new immune therapies that make T cells more effective at fighting disease.

Monocytes, however, are notoriously hard to study in the lab. Few of the cells circulate in the blood and they behave differently in a petri dish than they would inside the body. So, applying CRISPR-Cas9 to monocytes required tweaking the standard protocols. The team had to develop an approach that would not only alter the genes inside monocytes, but ensure that those edited cells were still functional.

“Editing monocytes was challenging, but we felt it was very important to replicate the success we had obtained with T cells in other immune cells,” says Joseph Hiatt, the study’s first author and a graduate student in the Marson and Krogan labs.

A Way to Study Infections

The group showed that the monocytes edited with their CRISPR-based approach could still give rise to both macrophages and dendritic cells. To confirm whether these new edited cells behaved normally, the researchers infected cells grown in the lab with the microbe that causes tuberculosis. Macrophages originating from edited monocytes, they found, were still capable of engulfing the pathogen.

The researchers next showed that using CRISPR-Cas9 to remove the gene SAMHD1 from monocytes–and therefore the resulting macrophages–boosted more than fifty-fold the infection of cells by HIV. While SAMHD1 was already known to protect human cells from HIV, the experiment confirmed the success of their gene-editing approach in monocytes and its promise for studying diseases.

Krogan’s lab has spent recent years cataloging human proteins that viruses use to infect cells and propagate. His research has included HIV, tuberculosis, Ebola virus, and Dengue virus–viruses known to target macrophages and dendritic cells. The new ability to edit genes in these cells will help his team validate their findings and identify vulnerabilities that may help combat these diseases in the future. It could also point toward targets for drugs that help boost the ability of monocytes to fight infections, or block viruses from hijacking monocytes in the first place.

“Now that we’re confident we can edit monocytes successfully, our approach will allow us to study these cells in depth, and understand their roles in infectious diseases,” says Devin Cavero, co-first author of the study and former UCSF research associate.


About the Study

The paper “Efficient Generation of Isogenic Primary Human Myeloid Cells Using CRISPR-Cas9 Ribonucleoproteins” was published by the journal Cell Reports on May 11, 2021:

Other authors are: Michael J. McGregor, Theodore L. Roth, Kelsey M. Haas, Ujjwal Rathore, Anke Meyer-Franke, Eric Shifrut, Youjin Lee, Vigneshwari Easwar Kumar, David E. Gordon, Jason A. Wojcechowskyj, Judd F. Hultquist, and Krystal A. Fontaine of Gladstone; Weihao Zheng, Jonathan M. Budzik, David Wu, Mohamed S. Bouzidi, Eric. V. Dang, Satish K. Pillai, and Joel D. Ernst of UC San Francisco; and Jeffery S. Cox of UC Berkeley.

The work was funded by the National Institutes of Health (P50 AI150476, U19 AI135990, P01 AI063302, R01 AI150449, and R01 AI124471) and the James B. Pendleton Charitable Trust.

The researchers involved are also supported in part by the National Science Foundation, a Ruth L. Kirschstein Fellowship, gifts from J. Aronov, G. Hoskin, K. Jordan, B. Bakar and the Caufield family, Gladstone, the Innovative Genomics Institute, the Parker Institute for Cancer Immunotherapy, a Career Award for Medical Scientists from the Burroughs Wellcome Fund, a Lloyd J. Old STAR award from the Cancer Research Institute, the Chan Zuckerberg Biohub, Vir Biotechnology, F. Hoffmann-LaRoche, and the BioFulcrum Viral and Infectious Disease Research Program at Gladstone.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes ( focuses on conditions with profound medical, economic, and social impact–unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.

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