A group of researchers with the Institute for Quantum Sciences and Engineering at Texas A&M University and the Texas A&M Engineering Experiment Station (TEES) have developed a new technique that allows low-concentration and low-dose screenings of protein-to-ligand interactions in physiologically relevant conditions. Titled thermostable-Raman-interaction-profiling (TRIP), this new approach is a paradigm-shifting answer to a long-standing problem that provides label-free, highly reproducible Raman spectroscopy measurements.

“Protein is a very fragile biological molecule and needs specific care,” said lead author and postdoctoral research assistant Dr. Narangerel Altangerel. “When I cool down the surface or substrate, I can make the proteins happy. I can poke them with the laser, and they can now output the information I need.”

While the proteins studied are on a molecular level, the implications of these findings could be huge. Like a lock and key, a protein-ligand interaction is the first step in processes like signal transduction, immune responses and gene regulation. Due to TRIP’s ability to detect protein-ligand interactions in real time, the timeline for drug and vaccine testing may be shortened. Another application could be clinical, turning lengthy tests to detect a virus into same-day turnaround with accurate results.

“The whole idea from the spectroscopy statute is that it requires minimum to none for sample preparation, so this can be moved into the clinic right away,” said co-author and University Professor in the Department of Biomedical Engineering Dr. Vladislav Yakovlev. “Clinicians and patients don’t have to wait for days and weeks of analysis. You can get all these answers almost right away.”

An additional benefit of the TRIP technique is that the sample size required to run the test is much smaller and requires a lower protein concentration, meaning a more cost-effective process for testing.

“I was buying 100 microliters of a sample for $3,500, then I have to share this sample with multiple people and end up with only a 20 to 30 microliter sample,” Altangerel said. “This forced me to use a smaller sample making Raman hard to do, as low-concentration samples make it a weak process. That made me challenge myself to try different things.”

Despite the breakthrough, the team is looking for other aspects in which the TRIP method could be useful.

“In a follow-up article, we are trying to identify the chemical composition of those proteins just using this technique so we can apply this to similar ideas related to DNA analysis and other biological molecules,” Yakovlev said. “Something that normally requires sequencing but utilizes TRIP, so you don’t need any sample preparation.”

The researchers published their findings in the Proceedings of the National Academy of Sciences. The project is supported by the Air Force Office of Scientific Research (AFOSR), the Office of Naval Research, the Robert A. Welch Foundation, TEES, the National Institutes of Health and the Texas A&M University X Grants Program.

The supporting team comprises faculty and students affiliated with the Institute for Quantum Sciences and Engineering. Additional authors credited are Dr. Benjamin Neuman in the Department of Biology, Dr. Philip Hemmer in the Department of Electric and Computer Engineering, Navid Rajil, Dr. Zhenhuan Yi, Dr. Alexei Sokolov and principal investigator Dr. Marlan Scully in the Institute for Quantum Sciences and Engineering. Dr. Sofi Bin-Salamon served as the program officer for the AFOSR.

“For a long time. people thought this is impossible to do,” Dr. Yakovlev said. “But Dr. Altangerel demonstrated that nothing, indeed, is impossible if you do things right.”

“These beans are preserved among Mayan communities and grown by indigenous farmers. They are heirlooms from past generations and are important because of their cultural significance and contribution to biodiversity,” explained study co-author Elvira de Mejia, professor in the Department of Food Science and Human Nutrition (FSHN), part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.

The research team selected two varieties among several collected in the Chiapas region because of their high phenolic content, present in the seed coat pigment that gives the beans their dark red or black coloring.

“These phenolic compounds have the capability of keeping oxidation and inflammation under control, which could help decrease the risk of chronic health issues such as cardiovascular disease, cancer, and diabetes,” de Mejia said.

First, the researchers removed the bean seed coat and ground it for processing. Then they analyzed the chemical composition of a crude extract, as well as an enriched extract that was purified to concentrate the phenolic content. They also measured the bean extracts’ antioxidant capacity and ability to inhibit free radicals through biochemical assays and in silico molecular docking, a type of computer simulation.

“We found the black beans had high quantities of anthocyanin, in particular delphinidin, petunidin, and malvidin glucosides, which have antioxidative properties. The pinto beans had the highest total content of phenolic compounds and showed great potential for inhibiting enzymes that contribute to inflammation,” said David Fonseca Hernández, a doctoral student at CIATEJ, and lead author of the paper. Fonseca conducted the research as a visiting scholar in FSHN at U. of I.

The seed coat extracts can be used as additives in the food industry or in cosmetics, Fonseca explained.

“My research focuses on skin health, because there is a lot of interest in new ingredients with bioactive properties to use in formulations for creams. One of the main issues with aging skin is the oxidative stress that results from environmental factors. When the skin is exposed to air pollution and sunlight, it produces higher quantities of free radicals and inflammation pathways are activated,” he stated.

“We tested some markers related to inflammation, such as cyclooxygenase and inducible nitric oxide synthase. We had really good results showing the extracts, especially from pinto beans, could inhibit and reduce the activity of these enzymes.”

The researchers also found that the process of enriching the extracts can further concentrate the anthocyanins and phenolic compounds, which is useful both for industry and research purposes.

The study is part of a large project supported by CONAHCYT, Mexico’s National Science Foundation, explained study co-author Luis Mojica, research professor at CIATEJ and Fonseca’s advisor.

“One of the project’s goals was to find cultivars with an interesting profile to be used as a source of phytochemicals for the cosmetic industry. This industry is growing very fast, and there is a demand for natural products to treat skin-related diseases or aging,” he said. “In our research, we compared around 60 cultivars of common beans from the south of Mexico, and these two varieties are three or four times higher than others in phenolic compounds and anthocyanins. These beans are very interesting for health; they are also high in other nutrients such as proteins, fiber, and oligosaccharides.”

The project can help provide regional support by increasing wellness and developing Mexico’s southern region by preserving these unique bean varieties, the researchers stated.

Following up on the study’s significant laboratory findings, the next steps will be to test the extracts on cell tissue cultures and eventually in clinical trials.

Fonseca attended the U. of I. through I-MMAS, a program created to increase recruitment of Mexican and Mexican-American students within the University of Illinois System.

“Our collaboration with Dr. Mojica’s research group through I-MMAS is meaningful because there is a large number of migrants from Guadalajara in Illinois, but also because of the quality of their work. Dr. Mojica’s lab conducts basic research, but they also work with industry to apply the knowledge to solve practical problems. Dr. Mojica completed his doctorate degree in FSHN at U. of I. Both he and David were very productive and successful students during their time here, and we are very happy to continue our work with them,” de Mejia concluded.

The paper, “Black and pinto beans (Phaseolus vulgaris L.) unique mexican varieties exhibit antioxidant and anti-inflammatory potential,” is published in Food Research International [DOI: 10.1016/j.foodres.2023.112816]. Authors are David Fonseca Hernández, Luis Mojica, Mark A. Berhow, Korey Brownstein, Eugenia Lugo Cervantes, and Elvira Gonzalez de Mejia.

Funding for this research was provided by the Consejo Nacional de Humanidades Ciencias y Tecnologías CONAHCYT-Mexico, number 901000 and FORDECYT grant number 292474, and by the U.S. Department of Agriculture, Agricultural Research Service.

In hopes of improving the overall survival rate for breast cancer patients, MIT researchers have designed a wearable ultrasound device that could allow people to detect tumors when they are still in early stages. In particular, it could be valuable for patients at high risk of developing breast cancer in between routine mammograms.

The device is a flexible patch that can be attached to a bra, allowing the wearer to move an ultrasound tracker along the patch and image the breast tissue from different angles. In the new study, the researchers showed that they could obtain ultrasound images with resolution comparable to that of the ultrasound probes used in medical imaging centers.

“We changed the form factor of the ultrasound technology so that it can be used in your home. It’s portable and easy to use, and provides real-time, user-friendly monitoring of breast tissue,” says Canan Dagdeviren, an associate professor in MIT’s Media Lab and the senior author of the study.

MIT graduate student Wenya Du, Research Scientist Lin Zhang, Emma Suh ’23, and Dabin Lin, a professor at Xi’an Technological University, are the lead authors of the paper, which appears today in Science Advances.

A wearable diagnostic

For this project, Dagdeviren drew inspiration from her late aunt, Fatma Caliskanoglu, who was diagnosed with late-stage breast cancer at age 49, despite having regular cancer screens, and passed away six months later. At her aunt’s bedside, Dagdeviren, then a postdoc at MIT, drew up a rough schematic of a diagnostic device that could be incorporated into a bra and would allow for more frequent screening of women at high risk for breast cancer.

Breast tumors that develop in between regularly scheduled mammograms — known as interval cancers — account for 20 to 30 percent of all breast cancer cases, and these tumors tend to be more aggressive than those found during routine scans.

“My goal is to target the people who are most likely to develop interval cancer,” says Dagdeviren, whose research group specializes in developing wearable electronic devices that conform to the body. “With more frequent screening, our goal to increase the survival rate to up to 98 percent.”

To make her vision of a diagnostic bra a reality, Dagdeviren designed a miniaturized ultrasound scanner that could allow the user to perform imaging at any time. This scanner is based on the same kind of ultrasound technology used in medical imaging centers, but incorporates a novel piezoelectric material that allowed the researchers to miniaturize the ultrasound scanner.

To make the device wearable, the researchers designed a flexible, 3D-printed patch, which has honeycomb-like openings. Using magnets, this patch can be attached to a bra that has openings that allow the ultrasound scanner to contact the skin. The ultrasound scanner fits inside a small tracker that can be moved to six different positions, allowing the entire breast to be imaged. The scanner can also be rotated to take images from different angles, and does not require any special expertise to operate.

“This technology provides a fundamental capability in the detection and early diagnosis of breast cancer, which is key to a positive outcome,” says Anantha Chandrakasan, dean of MIT’s School of Engineering, the Vannevar Bush Professor of Electrical Engineering and Computer Science, and one of the authors of the study. “This work will significantly advance ultrasound research and medical device designs, leveraging advances in materials, low-power circuits, AI algorithms, and biomedical systems.”

Early detection

Working with the MIT Center for Clinical and Translational Research, the researchers tested their device on one human subject, a 71-year-old woman with a history of breast cysts. Using the new device, the researchers were able to detect the cysts, which were as small as 0.3 centimeters in diameter — the size of early-stage tumors. They also showed that the device achieved resolution comparable to that of traditional ultrasound, and tissue can be imaged at a depth up to 8 centimeters.

“Access to quality and affordable health care is essential for early detection and diagnosis. As a nurse I have witnessed the negative outcomes of a delayed diagnosis. This technology holds the promise of breaking down the many barriers for early breast cancer detection by providing a more reliable, comfortable, and less intimidating diagnostic,” says Catherine Ricciardi, nurse director at MIT’s Center for Clinical and Translational Research and an author of the study.

To see the ultrasound images, the researchers currently have to connect their scanner to the same kind of ultrasound machine used in imaging centers. However, they are now working on a miniaturized version of the imaging system that would be about the size of a smartphone.

The wearable ultrasound patch can be used over and over, and the researchers envision that it could be used at home by people who are at high risk for breast cancer and could benefit from frequent screening. It could also help diagnose cancer in people who don’t have regular access to screening.

“Breast cancer is the most common cancer among women, and it is treatable when detected early,” says Tolga Ozmen, a breast cancer surgeon at Massachusetts General Hospital who is also an author of the study. “One of the main obstacles in imaging and early detection is the commute that the women have to make to an imaging center. This conformable ultrasound patch is a highly promising technology as it eliminates the need for women to travel to an imaging center.”

The researchers hope to develop a workflow so that once data are gathered from a subject, artificial intelligence can be used to analyze how the images change over time, which could offer more accurate diagnostics than relying on the assessment of a radiologist comparing images taken years apart. They also plan to explore adapting the ultrasound technology to scan other parts of the body.

The research was funded, in part, by the National Science Foundation, a 3M Non-Tenured Faculty Award, the Sagol Weizmann-MIT Bridge Program, and MIT Media Lab Consortium Funding

The study led by William Jaeger of the OSU College of Agricultural Sciences is based on an analysis of 50 years of data suggesting that while hatchery-reared salmon numbers have increased, there is no evidence of a net increase in wild, naturally spawning salmon and steelhead.

Findings were published today in PLOS One.

Jaeger, a professor of applied economics, notes that steelhead and Chinook, coho and sockeye salmon numbers have been under heavy pressure in the Columbia River Basin for more than a century and a half — initially from overharvesting, then from hydropower beginning in 1938 with the opening of Bonneville Dam, the lowermost dam on the mainstem Columbia.

“Also, farming, logging, mining and irrigation caused landscape changes and habitat degradation, which compounded the problems for the fish,” said Jaeger, who collaborated on the paper with Mark Scheuerell, a biologist with the U.S. Geological Survey and the University of Washington.

An estimated 16 million salmon and steelhead once returned from the Pacific to the portions of the basin above Bonneville Dam, but by the 1970s there were fewer than 1 million fish, prompting the federal government to intervene.

The Northwest Power Act of 1980 required fish and wildlife goals to be considered in addition to power generation and other objectives. The act created the Northwest Power and Conservation Council to set up conservation programs financed by Bonneville Power Administration revenues.

The cost and scale of restoration efforts grew considerably in the 1990s, Jaeger said, following the listing of 12 Columbia River runs of salmon and steelhead as threatened or endangered under the Endangered Species Act.

The public’s tab for conservation spending now exceeds $9 billion in inflation-adjusted 2020 U.S. dollars, the researchers said, which does not take into account all monies that have been spent by local governments and non-governmental agencies.

“The actual impact of all of these efforts has always been poorly understood,” Jaeger said. “Lots of people have long been concerned about a lack of evidence of salmon and steelhead recovery. One of the issues is that most studies evaluating restoration efforts have examined individual projects for specific species, life stages or geographic areas, which limits the ability to make broad inferences at the basin level.”

Thus, Jaeger notes, a key question has persisted, and its answer is critical for sound policy and legal decisions: Is there any evidence of an overall boost in wild fish abundance that can be linked to the totality of the recovery efforts?

Based on a half-century of fish return data at Bonneville Dam, the single entry point to the basin above the dam, the evidence does not support a yes answer.

“We found no evidence in the data that the restoration spending is associated with a net increase in wild fish abundance,” Jaeger said.

He said the Northwest Power and Conservation Council set a goal of increasing total salmon and steelhead abundance in the basin to 5 million fish by 2025, but annual adult returns at Bonneville Dam averaged less than 1.5 million in the 2010s.

And while hatchery production has helped with overall numbers of adult fish, Jaeger added, it has also adversely affected wild stocks through a range of mechanisms including genetics, disease, competition for habitat and food, and predation on wild fish by hatchery fish.

“The role of hatcheries in recovery plans is controversial for many reasons, but results do indicate that hatchery production combined with restoration spending is associated with increases in returning adult fish,” Jaeger said. “However, we found that adult returns attributable to spending and hatchery releases combined do not exceed what we can attribute to hatcheries alone. We looked at ocean conditions and other environmental variables, hatchery releases, survival rates for hatchery released fish, and conservation spending, and we saw no indication of a positive net effect for wild fish.”

Even expenditures on “durable” habitat improvements designed to cumulatively benefit naturally spawning wild salmon and steelhead over many years did not lead to evidence of a return on these investments, he added.

For the first time, scientists have managed to induce virgin birth in an animal that usually reproduces sexually: the fruit fly Drosophila melanogaster.

Once induced in this fruit fly, this ability is passed on through the generations: the offspring can reproduce either sexually if there are males around, or by virgin birth if there aren’t.

For most animals, reproduction is sexual — it involves a female’s egg being fertilised by a male’s sperm. Virgin birth, or ‘parthenogenesis’, is the process by which an egg develops into an embryo without fertilisation by sperm — a male is not needed.

The offspring of a virgin birth are not exact clones of their mother but are genetically very similar, and are always female.

“We’re the first to show that you can engineer virgin births to happen in an animal — it was very exciting to see a virgin fly produce an embryo able to develop to adulthood, and then repeat the process,” said Dr Alexis Sperling, a researcher at the University of Cambridge and first author of the paper.

She added: “In our genetically manipulated flies, the females waited to find a male for half their lives — about 40 days — but then gave up and proceeded to have a virgin birth.”

In the experiments, only 1-2% of the second generation of female flies with the ability for virgin birth produced offspring, and this occurred only when there were no male flies around. When males were available, the females mated and reproduced in the normal way.

Switching to a virgin birth can be a survival strategy: a one-off generation of virgin births can help to keep the species going.

The study is published today in the journal Current Biology.

To achieve their results, researchers first sequenced the genomes of two strains of another species of fruit fly, called Drosophila mercatorum. One strain needs males to reproduce, the other reproduces only through virgin birth. They identified the genes that were switched on, or switched off, when the flies were reproducing without fathers.

With the candidate genes for virgin birth ability identified in Drosophila mercatorum, the researchers altered what they thought were the corresponding genes in the model fruit fly, Drosophila melanogaster. It worked: Drosophila melanogaster suddenly acquired the ability for virgin birth.

The research involved over 220,000 virgin fruit flies and took six years to complete.

Key to the discovery was the fact that this work was done in Drosophila melanogaster — the researchers say it would have been incredibly difficult in any other animal. This fly has been the ‘model organism’ for research in genetics for over 100 years and its genes are very well understood.

Sperling, who carried out this work in the Department of Genetics, has recently moved to Cambridge Crop Science Centre to work on crop pests and hopes to eventually investigate why virgin birth in insects may be becoming more common, particularly in pest species.

“If there’s continued selection pressure for virgin births in insect pests, which there seems to be, it will eventually lead to them reproducing only in this way. It could become a real problem for agriculture because females produce only females, so their ability to spread doubles,” said Sperling.

The females of some egg-laying animals — including birds, lizards and snakes, can switch naturally to give birth without males. But virgin birth in animals that normally sexually reproduce is rare, often only observed in zoo animals, and usually happens when the female has been isolated for a long time and has little hope of finding a mate.

Parents the world over are prone to worry about their children getting either too little or too much sleep.

But a new study published today reveals that some children are more efficient at consolidating information during sleep, so they nap less frequently.

Meanwhile others, usually those with fewer words and poorer cognitive skills, need to nap more frequently.

The research team say that reducing naps for these children will not improve brain development, and that they should be allowed to nap as frequently and for as long as they need.

Lead researcher Dr Teodora Gliga said: “There is a lot of parental anxiety around sleep. Parents worry that their kids don’t nap as much as expected for their age — or nap too frequently and for too long.

“But our research shows that how frequently a child naps reflects their individual cognitive need. Some are more efficient at consolidating information during sleep, so they nap less frequently.

“Children with smaller vocabularies or a lower score in a measure of executive function, nap more frequently.

“Young children will naturally nap for as long as they need and they should be allowed to do just that,” she added.

The research team studied 463 infants aged between eight months and three years during lockdown in 2020.

Parents were surveyed about their children’s sleep patterns, their ability to focus on a task, keep information in their memory, and the number of words that they understood and could say.

They also asked parents about their socio-economic status — including their postcode, income, and education — and about the amount of screen time and outdoors activities their child engaged in.

Dr Gliga said: “Lockdown gave us an opportunity to study children’s intrinsic sleep needs because when children are in childcare, they rarely nap as much as they need to.

“Because nurseries were closed, it meant less disturbance to the children’s natural sleep patterns. None of the children taking part were attending day care.

“What we found is that the structure of daytime sleep is an indicator of cognitive development.

“Infants with more frequent but shorter naps than expected for their age had smaller vocabularies, and worse cognitive function.

“We also found that this negative association between vocabulary and frequency of naps was stronger in older children,” she added.

“While the majority of parents told us that their child’s sleep was unaffected by lockdown, parents from lower socio-economic backgrounds were more likely to report a worsening in sleep.

“Screen time increased during lockdown and outdoor activities decreased but these did not explain differences in children’s sleep.

“Previous work suggested that caregivers should encourage frequent naps, in pre-school children.

“Our findings suggest that children have different sleep needs — some children may drop naps earlier because they don’t need them anymore. Others may still need to nap past three years of age.

“In the UK, preschools enrolling three to five-year-olds have no provisions for napping. Caregivers should use a child’s mental age and not chronological age to ascertain a child’s sleep needs,” she added.

The study was led by UEA in collaboration with researchers at the University of Oxford, Oxford Brookes University, the University of Leeds and the University of Warwick. It was funded by the Economic and Social Research Council (ESRC).

‘More frequent naps are associated with lower cognitive development in a cohort of 8 to 38- month-old children, during the Covid-19 pandemic’ is published in the journal JCPP Advances.