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#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutGuidelines After VaccinationAdvertisementContinue reading the main storySupported byContinue reading the main storyThe U.S. Is Sitting on Tens of Millions of Vaccine Doses the World NeedsDoses from the drug maker AstraZeneca sit in U.S. manufacturing plants, awaiting regulatory authorization as the world goes begging.An Emergent BioSolutions laboratory in Baltimore. The company has already produced tens of millions of doses of the AstraZeneca vaccine, which cannot be used in the United States yet.Credit…Michael Robinson Chavez/The Washington Post, via Getty ImagesNoah Weiland and March 11, 2021, 6:25 p.m. ETWASHINGTON — Tens of millions of doses of the coronavirus vaccine made by the British-Swedish company AstraZeneca are sitting idly in American manufacturing facilities, awaiting results from its U.S. clinical trial while countries that have authorized its use beg for access.The fate of those doses of AstraZeneca’s vaccine is the subject of an intense debate among White House and federal health officials, with some arguing the administration should let them go abroad where they are desperately needed while others are not ready to relinquish them, according to senior administration officials.AstraZeneca is involved in those conversations.“We understand other governments may have reached out to the U.S. government about donation of AstraZeneca doses, and we’ve asked the U.S. government to give thoughtful consideration to these requests,” said Gonzalo Viña, a spokesman for AstraZeneca.About 30 million doses are currently bottled at AstraZeneca’s facility in West Chester, Ohio, which handles “fill-finish,” the final phase of the manufacturing process during which the vaccine is placed in vials, one official with knowledge of the stockpile said.Emergent BioSolutions, a company in Maryland that AstraZeneca has contracted to manufacture its vaccine in the United States, has also produced enough vaccine in Baltimore for tens of millions more doses once it is filled into vials and packaged, the official said.But although AstraZeneca’s vaccine is already authorized in more than 70 countries, according to a company spokesman, its U.S. clinical trial has not yet reported results, and the company has not applied to the Food and Drug Administration for emergency use authorization. AstraZeneca has asked the Biden administration to let it loan American doses to the European Union, where it has fallen short of its original supply commitments and where the vaccination campaign has stumbled badly.The administration, for now, has denied the request, one official said.Some federal officials have pushed the White House to make a decision in the next few weeks. Officials have discussed sending doses to Brazil, hard hit by a worsening coronavirus crisis.“If those donation actions were to proceed, we would seek guidance from the U.S. government on replacement of doses for use in the U.S.,” Mr. Viña said.The White House did not respond to a request for comment.The administration’s hesitation is at least partly related to uncertainties with vaccine supply before a benchmark of late May laid down by President Biden when he promised enough vaccine doses to cover every adult in the United States. Vaccine production is notoriously complex and delicate, and problems like mold growth can interrupt a plant’s progress.Last May, the Trump administration pledged up to $1.2 billion to AstraZeneca to finance the development and manufacturing of its vaccine, which it developed with the University of Oxford, and to supply the United States with 300 million doses if it proved effective. Federal officials and public health experts last year viewed the vaccine, which is less expensive and easier to store for long periods than some other vaccines, as most likely to be among the first to receive authorization.That never happened, in part because of a pattern of communication blunders by AstraZeneca that weakened the company’s relationship with American regulators and slowed the vaccine’s development. Last fall, AstraZeneca’s trial in the United States — the same one that will soon report results — was grounded for nearly seven weeks because the company was slow to provide the F.D.A. with evidence that the vaccine had not caused serious neurological side effects in two volunteers.The company is now grappling with another safety scare. Acting out of precaution, health authorities in Denmark, Norway and Iceland suspended use of the AstraZeneca’s vaccine on Thursday after several reports across the continent of severe blood clots.European official and the company said there was not evidence of any causal link. In the vast majority of cases, the emergence of such medical conditions has nothing to do with the vaccine. Some percentage of people are expected to fall ill by chance after getting vaccinated, as would happen in any group of people.The Coronavirus Outbreak

For the first time ever, a Northwestern University-led research team has peered inside a human cell to view a multi-subunit machine responsible for regulating gene expression.
Called the Mediator-bound pre-initiation complex (Med-PIC), the structure is a key player in determining which genes are activated and which are suppressed. Mediator helps position the rest of the complex — RNA polymerase II and the general transcription factors — at the beginning of genes that the cell wants to transcribe.
The researchers visualized the complex in high resolution using cryogenic electron microscopy (cryo-EM), enabling them to better understand how it works. Because this complex plays a role in many diseases, including cancer, neurodegenerative diseases, HIV and metabolic disorders, researchers’ new understanding of its structure could potentially be leveraged to treat disease.
“This machine is so basic to every branch of modern molecular biology in the context of gene expression,” said Northwestern’s Yuan He, senior author of the study. “Visualizing the structure in 3D will help us answer basic biological questions, such as how DNA is copied to RNA.”
“Seeing this structure allows us to understand how it works,” added Ryan Abdella, the paper’s co-first author. “It’s like taking apart a common household appliance to see how everything fits together. Now we can understand how the proteins in the complex come together to perform their function.”
The study will be published March 11 in the journal Science. This marks the first time the human Mediator complex has been visualized in 3D in the human cell.

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He is an assistant professor of molecular biosciences in Northwestern’s Weinberg College of Arts and Sciences. Abdella and Anna Talyzina, both graduate students in the He lab, are co-first authors of the paper.
Famed biochemist Roger Kornberg discovered the Mediator complex in yeast in 1990, a project for which he won the 2006 Nobel Prize in Chemistry. But Mediator comprises a daunting 26 subunits — 56 total when combined with the pre-initiation complex — it’s taken researchers until now to obtain high-resolution images of the human version.
“It’s a technically quite challenging project,” He said. “These complexes are scarce. It takes hundreds of liters of human cells, which are very hard to grow, to obtain small amounts of the protein complexes.”
A breakthrough came when He’s team put the sample on a single layer of graphene oxide. By providing this support, the graphene sheet minimized the amount of sample needed for imaging. And compared to the typical support used — amorphous carbon — graphene improved the signal-to-noise ratio for higher-resolution imaging.
After preparing the sample, the team used cryo-EM, a relatively new technique that won the 2017 Nobel Prize in Chemistry, to determine the 3D shape of proteins, which are often thousands of times smaller than the width of a human hair. The technique works by blasting a stream of electrons at a flash-frozen sample to take many 2D images.

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For this study, He’s team captured hundreds of thousands of images of the Med-PIC complex. They then used computational methods to reconstruct a 3D image.
“Solving this complex was like assembling a puzzle,” Talyzina said. “Some of those subunits were already known from other experiments, but we had no idea how the pieces assembled together or interacted with each other. With our final structure, we were finally able to see this whole complex and understand its organization.”
The resulting image shows the Med-PIC complex as a flat, elongated structure, measuring 45 nanometers in length. The researchers also were surprised to discover that the Mediator moves relative to the rest of the complex, binding to RNA polymerase II at a hinge point.
“Mediator moves like a pendulum,” Abdella said. “Next, we want to understand what this flexibility means. We think it might have an impact on the activity of a key enzyme within the complex.”
The paper was supported by Northwestern’s Chemistry of Life Sciences Institute, the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust, the American Cancer Society (award number IRG-15-173-21), the H Foundation (award number U54-CA193419) and the National Institutes of Health (award numbers R01-GM135651 and P01-CA092584).

Breast cancer is harmful enough on its own, but when cancer cells start to metastasize — or spread into the body from their original location — the disease becomes even more fatal and difficult to treat.
Thanks to new research published in Oncogene from the lab of University of Colorado Cancer Center associate director of basic research Heide Ford, PhD, in collaboration with Michael Lewis, PhD, from Baylor College of Medicine, doctors may soon have a better understanding of one mechanism by which metastasis happens, and of potential ways to slow it down.
“Metastasis is a huge problem nobody’s tackled very well,” says Ford, who holds the Grohne Endowed Chair in Cancer Research at the University of Colorado School of Medicine. “People don’t know how to inhibit the process of metastasis, nor how to inhibit the growth of metastatic cells at secondary sites. And that’s what kills most cancer patients. A lot of common drugs, whether they’re targeted drugs or chemotherapies that are less targeted, do pretty well at inhibiting the primary tumor, but by the time cells metastasize, they’ve changed enough that they don’t get inhibited by those drugs.”
The transformation Ford and her team are studying happens when cells called epithelial cells, which are more adherent to one another and less likely to spread to other parts of the body, start to take on the characteristics of mesenchymal cells, which are more migratory and more likely to invade other parts of the body. This transformation is referred to as the epithelial-to-mesenchymal transition.
“When the epithelial cancer cells take on these characteristics of mesenchymal cells, they become less attached to their neighbor and they become more able to degrade membranes, so they can get into the bloodstream more easily,” Ford says.
In 2017, Ford published a paper showing that the metastasis process is helped along when cells that have undergone the epithelial-to-mesenchymal transition start “talking” to cells that haven’t, making those cells more likely to gain metastatic properties.
In a new paper published in December, Ford and her researchers, in a collaborative study done with Lewis and colleagues at Baylor College of Medicine, posit that the crosstalk is facilitated by a naturally occurring protein called VEGF-C.
“VEGF-C is secreted by the cells. It binds to receptors on these neighboring cells and then activates a pathway called the hedgehog signaling pathway, though it bypasses the traditional way of activating this pathway,” Ford says. “That turns on a signaling mechanism that ultimately results in activation of a protein called GLI that makes these cells more invasive and more migratory.”
In their new paper, Ford, Lewis and their researchers show that if you can inhibit production of VEGF-C, you can significantly slow metastasis.
“If you take out the receptor that receives the signal from the cells that have not undergone a transition, or if you take VEGF-C out of the mix, you can’t stimulate metastasis to the same degree,” she says. “If you remove that ability for these different cell types to crosstalk, now these cells that never underwent a transition can’t move as well anymore. They can’t metastasize as efficiently.”
The researchers are now in the early stages of animal trials to find out the best way to target that signaling pathway in order to better inhibit metastasis. They want to find out if they can stop metastasis from happening at all, and if they can slow its progression in patients in whom the metastatic process has already begun — and to see if they can inhibit tumor growth at the secondary site.
“For many years, people said there was no point in finding inhibitors to metastasis because by the time someone comes into the clinic, the horse is out of the barn, so to speak. The cells have already gotten out of the primary tumor and you can’t do anything about it,” Ford says. “But that’s not necessarily true. Now, data show that if you have cells that have metastasized to a second site — say you have breast cancer and the cells went into the lungs — those cells that are in the lungs could in fact start metastasizing to other sites. You want to stop that process no matter where you are in this progression.”

A new study demonstrates that machine-learning strategies can be applied to routinely collected physiological data, such as heart rate and blood pressure, to provide clues about pain levels in people with sickle cell disease. Mark Panaggio of Johns Hopkins University Applied Physics Laboratory and colleagues present these findings in the open-access journal PLOS Computational Biology.
Pain is subjective, and monitoring pain can be intrusive and time-consuming. Pain medication can help, but accurate knowledge of a patient’s pain is necessary to balance relief against risk of addiction or other unwanted effects. Machine-learning strategies have shown promise in predicting pain from objective physiological measurements, such as muscle activity or facial expressions, but few studies have applied machine learning to routinely collected data.
Now, Panaggio and colleagues have developed and applied machine-learning models to data from people with sickle cell disease who were hospitalized due to debilitating pain. These statistical models classify whether a patient’s pain was low, moderate, or high at each point during their stay based on routinely collected measurements of their blood pressure, heart rate, temperature, respiratory rate, and oxygen levels.
The researchers found that these vital signs indeed gave clues into the patients’ reported pain levels. By taking physiological data into account, their models outperformed baseline models in estimating subjective pain levels, detecting changes in pain, and identifying atypical pain levels. Pain predictions were most accurate when they accounted for changes in patients’ vital signs over time.
“Studies like ours show the potential that data-driven models based on machine learning have to enhance our ability to monitor patients in less invasive ways and ultimately, be able to provide more timely and targeted treatments,” Panaggio says.
Looking ahead, the researchers hope to leverage more comprehensive data sources and real-time monitoring tools, such as fitness trackers, to build better models for inferring and forecasting pain.

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Insights into how bacterial proteins work as a network to take control of our cells could help predict infection outcomes and develop new treatments.
Much like a hacker seizes control of a company’s software to cause chaos, disease-causing bacteria, such as E. coli and Salmonella, use miniature molecular syringes to inject their own chaos-inducing agents (called effectors) into the cells that keep our guts healthy.
These effectors take control of our cells, overwhelming their defences and blocking key immune responses, allowing the infection to take hold.
Previously, studies have investigated single effectors. Now a team led by scientists at Imperial College London and The Institute of Cancer Research, London, and including researchers from the UK, Spain and Israel, has studied whole sets of effectors in different combinations.
The study, published today in Science, investigated data from experiments in mice infected with the mouse version of E. coli, called Citrobacter rodentium, which injects 31 effectors.
The results show how effectors work together as a network, allowing them to colonise their hosts even if some effectors are removed. The investigation also revealed how the host’s immune system can bypass the obstacles the effectors create, triggering complementary immune responses.

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The researchers suggest that knowing how the makeup of effector networks influences the ability of infections to take hold could help design interventions that disrupt their effects.
Study lead Professor Gad Frankel, from the Department of Life Sciences at Imperial, said: “The data represent a breakthrough in our understanding of the mechanisms of bacterial infections and host responses. Our results show that the injected effectors are not working individually, but instead as a pack.
“We found there is an inherent strength and flexibility to the network, which ensures that if one or several components don’t work, the infection can go on. Importantly, this work has also revealed that our cells have a built-in firewall, which means that we can deal with the hacker’s corruptive networks and mount effective immune responses that can clear the infection.”
Study co-lead Professor Jyoti Choudhary, from the Functional Proteomics Lab at The Institute of Cancer Research, London, said: “Our study shows that we can predict how a cell will respond when attacked by different combinations of bacterial effector proteins. The research will help us to better understand how cells, the immune system and bacteria interact, and we can apply this knowledge to diseases like cancer and inflammatory bowel disease where bacteria in the gut play an important role.
“We hope, through further study, to build on this knowledge and work out exactly how these effector proteins function, and how they work together to disrupt host cells. In future, this enhanced understanding could lead to the development of new treatments.”
During their experiments, the team were able to remove different effectors when infecting mice with the pathogen, tracking how successful each infection was. This showed that the effector network produced by the pathogen could be reduced by up to 60 percent and still produce a successful infection.

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The team collected data on more than 100 different synthetic combinations of the 31 effectors, which Professor Alfonso Rodríguez-Patón and Elena Núñez-Berrueco at the Universidad Politécnica de Madrid used to build an artificial intelligence (AI) algorithm.
The AI model was able to predict the outcomes of infection with Citrobacter rodentium expressing different effector networks, which were tested with experiments in mice. As it is impossible to test in the lab all the possible networks that 31 effectors can form, employing an AI model is the only practical approach to studying biological systems of this complexity.
Co-first author Dr David Ruano-Gallego from the Department of Life Sciences at Imperial, said: “The AI allows us to focus on creating the most relevant combinations of effectors and learn from them how bacteria are counteracted by our immune system. These combinations would not be obvious from our experimental results alone, opening up the possibility of using AI to predict infection outcomes.”
Co-first author Dr Julia Sánchez-Garrido, from the Department of Life Sciences at Imperial, added: “Our results also mean that in the future, using AI and synthetic biology, we should be able to work out which cell functions are essential during infection, enabling us to find ways to fight the infection not by killing the pathogen with antibiotics, but instead by changing and improving our natural defence responses to infection.”
This project was supported by The Wellcome Trust.

An enzyme called MARK2 has been identified as a key stress-response switch in cells in a study by researchers at Johns Hopkins Bloomberg School of Public Health. Overactivation of this type of stress response is a possible cause of injury to brain cells in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis. The discovery will make MARK2 a focus of investigation for its possible role in these diseases, and may ultimately be a target for neurodegenerative disease treatments.
In addition to its potential relevance to neurodegenerative diseases, the finding is an advance in understanding basic cell biology.
The paper describing the discovery appears online March 11 in PLoS Biology.
The study focused on the cellular response to “proteotoxic” stress — a buildup of damaged or aggregated proteins within the main part of the cell, which is a central feature of neurodegenerative diseases. It has been known that cells respond to this type of stress by reducing their production of new proteins, and that a signaling enzyme likely mediates this response. The researchers, after ruling out other signaling enzymes, were able to show that the signaling enzyme MARK2 has this role.
“Further studies of this previously unrecognized signaling pathway should expand our understanding of protein regulation in cells and the role of this process in the development of human diseases,” says Jiou Wang, PhD, a professor in the Department of Biochemistry and Molecular Biology at the Bloomberg School.
Together, Alzheimer’s, ALS, and other neurodegenerative disorders afflict well over 50 million people worldwide. To date there is no disease-slowing treatment, let alone a cure, for any of them — primarily because their causes are not well understood.

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One possible set of causes of neurodegenerative disorders relates to the proteotoxic stress and the response in brain cells. When this response is activated, reducing protein synthesis, it ideally minimizes the protein burden of the cell under proteotoxic stress, thereby allowing it to recover from the stress. But the long-term reduction of protein synthesis could end up starving the cell of needed proteins, injuring it, and potentially triggering cell death. In other cases, the failure of the proteotoxic stress response, rather than its overactivation, may be the problem, so that protein overload leads to cell injury or death.
To fully understand either scenario, scientists need to understand the signaling pathway that senses proteotoxic stress and switches on the proteotoxic stress response. Wang and colleagues in their new study set out to discover it.
Like others in this field, the research team already knew that the molecule at the end of this pathway that switches off protein production is a member of a broad class of signaling enzymes called kinases. They also knew in advance that there are several specific kinases that switch off protein production in the same way, but in response to other types of cellular stress, such as viral infection. The challenge in this study was to find the specific kinase that throws this switch in response to proteotoxic stress in the main part of the cell.
The researchers first identified the kinase MARK2 as one of several candidates for their inquiry by sifting through a large database, produced with prior research, of various kinases and the proteins they potentially act upon. Following up their leads with various cell-free and cell culture experiments, they were able to show that MARK2, and no other candidate kinase, can switch off the protein-making machinery in cells in response to proteotoxic stress, even when the other four known protein-shutdown kinases are absent.
Looking upstream in the signaling pathway, the team found that MARK2 is activated by another signaling kinase, PKCδ, which becomes available for its MARK2-activating role under conditions of proteotoxic stress, thus effectively acting as a proteotoxic stress sensor.
As a preliminary check on the clinical relevance of these findings, the researchers examined a mouse model of familial ALS and samples of spinal cord tissue from human ALS patients. They found evidence that this PKCδ-MARK2 pathway is highly active in these cases compared to non-ALS mice and humans.
“These findings are consistent with the idea that in ALS, for example, this PKCδ-MARK2 pathway is highly active and reducing protein production, which over the long term contributes to the disease process,” Wang says.
Having clarified the basics of how this pathway works, Wang and colleagues are now planning to study it in different neurodegenerative disease models to determine whether the pathway could be targeted to treat such diseases.
“I suspect that this PKCδ-MARK2 pathway will ultimately be shown to be relevant not only in neurodegenerative disorders but in many other diseases including cancers,” Wang says.

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutGuidelines After VaccinationAdvertisementContinue reading the main storyCovid-19 News: A Year After W.H.O. Declared Virus Pandemic, More U.S. States Expand Access to VaccinesFor a second St. Patrick’s Day without parades, some places find other ways to celebrate.March 11, 2021, 3:23 p.m. ETMarch 11, 2021, 3:23 p.m. ETPeople waved a flag in celebration of St. Patrick’s Day last year, despite the cancellation of the parade in New York because of the pandemic. Celebrations around the country will again be cancelled this year.Credit…Spencer Platt/Getty ImagesThe pandemic in the United States, now more than a year old, is starting to hit some calendar milestones for a second time, including St. Patricks’ Day parades across the country. The sudden cancellation of the parades last year was one of the first big signs of how disruptive the pandemic would be to normal life in the U.S.Though many states and cities have been tentatively loosening various Covid restrictions lately, most places have not cleared the way for a resumption of parades, which can be among the most ruthlessly effective kinds of super-spreading events.So the St. Patrick’s Day parade in Chicago has been canceled, again; the parade in Boston canceled, again; the one in Philadelphia, canceled, again. The parade in New York City, intent on retaining its distinction as the oldest uninterrupted St. Patrick’s Day parade in the world, will once again be largely ceremonial and very low-profile, with a small group walking up Fifth Avenue at an unannounced time very early in the morning — that is, if the city and state approve doing anything at all.Some places are putting a spin on the commemorations. The 37th annual parade in St. James, on Long Island, is now going to be held by car; the one in Hilton Head, S.C., is moving to the water; and the one in Pittsburgh is moving to the fall (maybe). A drive-in Celtic rock concert is planned in Dublin, Calif.; a virtual 5K run in Naperville, Ill.; and a day of green beer in plastic cups being delivered by masked servers between plexiglass screens at McGillin’s Olde Ale House in Philadelphia.Last year, bars from Chicago to New Orleans were packed on the weekend before St. Patrick’s Day despite the cancellation of local parades, prompting stern admonitions from mayors and governors. This year, officials are pleading with people to stay at home, or at least to be vigilant when they are out.“We are not at a point where we can start having major St. Patrick’s Day celebrations,” Dr. Allison Arwady, the commissioner of the Chicago Department of Public Health, said to reporters in a recent briefing.The Coronavirus Outbreak

How do you turn “dumb” headphones into smart ones? Rutgers engineers have invented a cheap and easy way by transforming headphones into sensors that can be plugged into smartphones, identify their users, monitor their heart rates and perform other services.
Their invention, called HeadFi, is based on a small plug-in headphone adapter that turns a regular headphone into a sensing device. Unlike smart headphones, regular headphones lack sensors. HeadFi would allow users to avoid having to buy a new pair of smart headphones with embedded sensors to enjoy sensing features.
“HeadFi could turn hundreds of millions of existing, regular headphones worldwide into intelligent ones with a simple upgrade,” said Xiaoran Fan, a HeadFi primary inventor. He is a recent Rutgers doctoral graduate who completed the research during his final year at the university and now works at Samsung Artificial Intelligence Center.
A peer-reviewed Rutgers-led paper on the invention, which results in “earable intelligence,” will be formally published in October at MobiCom 2021, the top international conference on mobile computing and mobile and wireless networking.
Headphones are among the most popular wearable devices worldwide and they continue to become more intelligent as new functions appear, such as touch-based gesture control, the paper notes. Such functions usually rely on auxiliary sensors, such as accelerometers, gyroscopes and microphones that are available on many smart headphones.
HeadFi turns the two drivers already inside all headphones into a versatile sensor, and it works by connecting headphones to a pairing device, such as a smartphone. It does not require adding auxiliary sensors and avoids changes to headphone hardware or the need to customize headphones, both of which may increase their weight and bulk. By plugging into HeadFi, a converted headphone can perform sensing tasks and play music at the same time.
The engineers conducted experiments with 53 volunteers using 54 pairs of headphones with estimated prices ranging from $2.99 to $15,000. HeadFi can achieve 97.2 percent to 99.5 percent accuracy on user identification, 96.8 percent to 99.2 percent on heart rate monitoring and 97.7 percent to 99.3 percent on gesture recognition.

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To highlight tumours in the body for cancer diagnosis, doctors can use tiny optical probes (nanoprobes) that light up when they attach to tumours. These nanoprobes allow doctors to detect the location, shape and size of cancers in the body.
Most nanoprobes are fluorescent; they absorb light of a specific colour, like blue and then emit back light of a different colour, like green. However, as tissues of the human body can emit light as well, distinguishing the nanoprobe light from the background light can be tough and could lead to the wrong interpretation.
Now, researchers at Imperial College London have developed new nanoprobes, named bioharmonophores and patented at Imperial, which emit light with a new type of glowing technology known as second harmonic generation (SHG).
After testing the nanoprobes in zebrafish embryos, the researchers found that bioharmonophores, which were modified to target cancer cells, highlighted tumours more brightly and for longer periods than fluorescent nanoprobes. Their light can be easily spotted and distinguished by the tissue generally emitted light, and they also attach precisely to tumour cells and no healthy cells, making them more precise in detecting tumour edges.
Lead researcher Dr Periklis Pantazis of Imperial’s Department of Bioengineering said: “Bioharmonophores could be a more effective way to detect tumours than is currently available. They uniquely combine features that could be great for cancer diagnosis and therapy in clinical practice and could eventually improve patient outcomes following further research.”
The findings are published in ACS Nano.

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Bioharmonophores are both biocompatible and biodegradable as they are made of peptides — the same ingredients of proteins found in the body. They are metabolised naturally in the body within 48 hours and are therefore unlikely to pose long-term health risks.
To investigate precise tumour detection, the researchers first injected zebrafish embryos with malignant cancer cells, which allowed tumour cells to proliferate unchecked. Twenty-four hours later they injected bioharmonophores which were modified to target p32 peptide molecules that are specifically found in tumour cells. They then used imaging techniques at Imperial’s Facility for Imaging by Light Microscopy to study how well the modified bioharmonophores detected the tumours.
They found that bioharmonophores had outstanding detection sensitivity, meaning they attached to specific tumour cells but not to healthy ones. Fluorescence-enabled nanoprobes tend to attach less specifically, meaning they can misrepresent healthy cells as tumour cells, or vice versa.
They also found that unlike fluorescence, bioharmonophores did not ‘bleach’, meaning they did not lose their ability to emit light over time. In addition, the light emitted by bioharmonophores did not saturate as happens with fluorescent nanoprobes, meaning they got brighter when illuminated with more light. This way tumours became even clearer.
Dr Pantazis said: “It is very important that tumour nanoprobes highlight cells specifically and clearly for cancer diagnosis. Our proof-of-concept study suggests that the very bright bioharmonophores could be powerful tools in diagnosing cancer and targeting treatments in the coming years.”
The manufacture of bioharmonophores is cheap, reproducible, scalable and takes around two days at room temperature. They now need to be tested in mammals to identify how well the findings translate beyond zebrafish.
The researchers are also looking into how bioharmonophores could be used to guide surgical interventions during cancer surgery, as well as how they could generate light at different frequencies to potentially help kill tumour cells with high precision.
This work was funded by the Royal Society, Wellcome Trust, the Swiss National Science Foundation, the European Union, and the Swiss National Centre of Competence in Research.

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Researchers from Children’s Hospital of Philadelphia (CHOP) have determined what happens at a cellular level as the lung alveolus forms and allows newborns to breathe air. Understanding this process gives researchers a better sense of how to develop therapies and potentially regenerate this critical tissue in the event of injury. The findings were published online today by the journal Science.
The lung develops during both embryonic and postnatal stages, during which lung tissue forms and a variety of cell types perform specific roles. During the transition from embryo to newborn is when the alveolar region of the lung refines its primary function of exchanging gas, which includes the critical process of ridding the body of carbon dioxide.
Despite these critical steps involved in the formation of the lung, little is known about what happens at a cellular and genomic level. Not only is the lung alveolar critical, it can also suffer damage caused by pathogens such as influenza and the SARS-CoV2 virus that causes COVID-19. Knowing which cells are involved in the formation of healthy lung tissue at birth may provide a basis for therapies that help regenerate this critical portion of the lung.
“Extensive morphological changes properly shape the alveolar niche, but prior to this study, the research community was unsure as to the extent of cellular signaling involved to promote its proper architecture,” said first author Jarod A. Zepp, PhD, a research faculty member of the Division of Pulmonary and Sleep Medicine at CHOP and an Assistant Professor at the Perelman School of Medicine at the University of Pennsylvania. “Recent advances in technology allowed us to assess the intracellular communication that drives the generation of this critical portion of the lung.”
The study team used a multimodal approach to investigate intercellular relationships that drive the formation of the alveolus. They discovered that alveolar type 1 (AT1) epithelial cells, which form the outer layer of the alveolus tissue, represent a signaling hub that coordinates cell development, especially during the transition to air breathing. They also traced the lineage of AT1 cells and show that they align with myofibroblasts, which are a special cell type involved in tissue remodeling. Finally, the researchers also demonstrated that AT1-restricted ligands, or secreted binding molecules, are required to form these myofibroblasts and the alveolus.
“Our study reveals the complexity of the cell-types and their extensive communication with one another as they form this critical part of the lung,” Zepp said. “The recent COVID-19 pandemic has provided the research community with an increased appreciation of the intercellular communication that helps form the alveolar structure and maintain its function and provides us with vital clues on how we might be able to repair damaged tissue at a cellular level.”

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