“When viruses infect cells, they usually create specialized compartments — replication factories — where they form new viruses that infect more cells causing the disease,” said first author Dr. Soni Kaundal, postdoctoral associate in the Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology at Baylor in the lab of Dr. B.V. Venkataram Prasad, corresponding author of the work. “However, little is known about norovirus’s replication factories.

Increasing evidence shows that some replication factories typically are not separated from their surroundings by a membrane. Instead, they are biomolecular condensates, structures resembling a bubble formed by liquid-liquid phase separation. These condensates selectively incorporate proteins and other materials needed for viral replication. Liquid-like condensates as replication factories have been extensively studied in other viruses, including the rabies and measles viruses. In this study the researchers investigated whether norovirus forms biomolecular condensates that serve as replication hubs.

“We knew that these condensates are often initiated by a single viral protein capable of binding genetic material, having a flexible region and forming oligomers, molecules made of small numbers of repeating units,” Kaundal said.

The team began their investigation by applying bioinformatic analysis to identify norovirus proteins that would present the characteristics most likely leading to the formation of liquid condensates.

“Working with the human norovirus pandemic strain GII.4, the one responsible for causing most cases of gastroenteritis around the world, we found that the RNA-dependent RNA polymerase has the highest propensity to form biomolecular condensates,” Kaundal said. “This protein has a flexible region, can form oligomers, binds RNA, the norovirus’s genetic material, and plays an essential role during viral replication making copies of the viral RNA. All these characteristics prompted us to experimentally test whether the GII.4 RNA polymerase drives the formation of biomolecular condensates conducive to viral replication.”

“Our experimental studies show that GII.4 RNA polymerase indeed forms highly dynamic liquid-like condensates at physiologically relevant conditions in the lab and that the flexible region of this protein is critical for this process,” said Prasad, professor of molecular virology and microbiology and Alvin Romansky Chair in Biochemistryat Baylor. Prasad also is a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. “Furthermore, the condensates are highly dynamic structures: several can merge forming a larger structure or they can divide into smaller ones; they also move inside the cell, exchanging materials with their surroundings.”

Next, the researchers investigated whether these liquid-like condensates are also formed in human norovirus-infected human intestinal cells. Until recently, studying how norovirus replicates inside cells has been difficult because researchers lacked an effective biological system in which to grow the virus in the lab. But in 2016, the lab of Dr. Mary Estes at Baylor and colleagues succeeded at cultivating human norovirus strains in human intestinal enteroid cultures.

Also known as mini-guts, these cultures are a laboratory model of the human gastrointestinal tract that recapitulates its cellular complexity, diversity and physiology. Human enteroids mimic strain-specific host-virus infection patterns, making them an ideal system to dissect human norovirus infection, as in the current study, to identify strain-specific growth requirements and develop and test treatments and vaccines.

“We showed that liquid-like condensates are formed in human norovirus-infected human intestinal enteroid cultures as well as in the HEK293T human cell line grown in the lab. We propose that these condensates are replication hubs for human norovirus, an elegant solution to the puzzling question of how ribosome-assisted translation of the viral genome is segregated from its replication by the viral polymerase in positive-strand RNA viruses,” Prasad said. “Our bioinformatics analysis also showed that the RNA polymerases of almost all the norovirus strains have a high propensity to form these replication factories, suggesting that this may be a common phenomenon of most noroviruses.”

“This is a remarkable paper, and I was glad we could validate the findings in virus-infected cells using our human intestinal enteroids cultivation system for human norovirus,” said Estes, Distinguished Service Professor and Cullen Foundation Endowed Chair of molecular virology and microbiology at Baylor. Estes also is the co-director of the Gastrointestinal Experimental Model Systems core at the Texas Medical Center Digestive Diseases Center and a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

The findings not only provide new insight into human norovirus replication but also open new targets for designing antivirals for human norovirus infections, which remain a serious threat in children and immunocompromised patients.

Other contributors to this work include Ramakrishnan Anish, B. Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E. Crawford, Jeroen Pollet and Fabio Stossi. The authors are affiliated with Baylor College of Medicine and the University of Texas, MD Anderson Cancer Center.

Support for this project was provided by NIH grant P01 AI057788, Robert Welch Foundation grant Q1279, the Center for Advanced Microscopy and Image Informatics (Cancer Prevention and Research Institute of Texas (CPRIT) grant RP170719), the Integrated Microscopy Core at Baylor College of Medicine (NIH grants: DK56338, CA125123, ES030285 and S10OD030414), and CPRIT grant RR160029.

But devices that record electrical signals in cell cultures and other liquid environments often use wires to connect each electrode on the device to its respective amplifier. Because only so many wires can be connected to the device, this restricts the number of recording sites, limiting the information that can be collected from cells.

MIT researchers have now developed a biosensing technique that eliminates the need for wires. Instead, tiny, wireless antennas use light to detect minute electrical signals.

Small electrical changes in the surrounding liquid environment alter how the antennas scatter the light. Using an array of tiny antennas, each of which is one-hundredth the width of a human hair, the researchers could measure electrical signals exchanged between cells, with extreme spatial resolution.

The devices, which are durable enough to continuously record signals for more than 10 hours, could help biologists understand how cells communicate in response to changes in their environment. In the long run, such scientific insights could pave the way for advancements in diagnosis, spur the development of targeted treatments, and enable more precision in the evaluation of new therapies.

“Being able to record the electrical activity of cells with high throughput and high resolution remains a real problem. We need to try some innovative ideas and alternate approaches,” says Benoît Desbiolles, a former postdoc in the MIT Media Lab and lead author of a paper on the devices.

He is joined on the paper by Jad Hanna, a visiting student in the Media Lab; former visiting student Raphael Ausilio; former postdoc Marta J. I. Airaghi Leccardi; Yang Yu, a scientist at Raith America, Inc.; and senior author Deblina Sarkar, the AT&T Career Development Assistant Professor in the Media Lab and MIT Center for Neurobiological Engineering and head of the Nano-Cybernetic Biotrek Lab. The research appears today in Science Advances.

“Bioelectricity is fundamental to the functioning of cells and different life processes. However, recording such electrical signals precisely has been challenging,” says Sarkar. “The organic electro-scattering antennas (OCEANs) we developed enable recording of electrical signals wirelessly with micrometer spatial resolution from thousands of recording sites simultaneously. This can create unprecedented opportunities for understanding fundamental biology and altered signaling in diseased states as well as for screening the effect of different therapeutics to enable novel treatments.”

Biosensing with light

The researchers set out to design a biosensing device that didn’t need wires or amplifiers. Such a device would be easier to use for biologists who may not be familiar with electronic instruments.

“We wondered if we could make a device that converts the electrical signals to light and then use an optical microscope, the kind that is available in every biology lab, to probe these signals,” Desbiolles says.

Initially, they used a special polymer called PEDOT:PSS to design nanoscale transducers that incorporated tiny pieces of gold filament. Gold nanoparticles were supposed to scatter the light — a process that would be induced and modulated by the polymer. But the results weren’t matching up with their theoretical model.

The researchers tried removing the gold and, surprisingly, the results matched the model much more closely.

“It turns out we weren’t measuring signals from the gold, but from the polymer itself. This was a very surprising but exciting result. We built on that finding to develop organic electro-scattering antennas,” he says.

The organic electro-scattering antennas, or OCEANs, are composed of PEDOT:PSS. This polymer attracts or repulses positive ions from the surrounding liquid environment when there is electrical activity nearby. This modifies its chemical configuration and electronic structure, altering an optical property known as its refractive index, which changes how it scatters light.

When researchers shine light onto the antenna, the intensity of the light it scatters back changes in proportion to the electrical signal present in the liquid.

With thousands or even millions of tiny antennas in an array, each only 1 micrometer wide, the researchers can capture the scattered light with an optical microscope and measure electrical signals from cells with high resolution. Because each antenna is an independent sensor, the researchers do not need to pool the contribution of multiple antennas to monitor electrical signals, which is why OCEANs can detect signals with micrometer resolution.

Intended for in vitrostudies, OCEAN arrays are designed to have cells cultured directly on top of them and put under an optical microscope for analysis.

“Growing” antennas on a chip

Key to the devices is the precision with which the researchers can fabricate arrays in the MIT.nano facilities.

They start with a glass substrate and deposit layers of conductive then insulating material on top, each of which is optically transparent. Then they use a focused ion beam to cut hundreds of nanoscale holes into the top layers of the device. This special type of focused ion beam enables high-throughput nanofabrication.

“This instrument is basically like a pen where you can etch anything with a 10-nanometer resolution,” he says.

They submerge the chip in a solution that contains the precursor building blocks for the polymer. By applying an electric current to the solution, that precursor material is attracted into the tiny holes on the chip, and mushroom-shaped antennas “grow” from the bottom up.

The entire fabrication process is relatively fast, and the researchers could use this technique to make a chip with millions of antennas.

“This technique could be easily adapted so it is fully scalable. The limiting factor is how many antennas we can image at the same time,” he says.

The researchers optimized the dimensions of the antennas and adjusted parameters, which enabled them to achieve high enough sensitivity to monitor signals with voltages as low as 2.5 millivolts in simulated experiments. Signals sent by neurons for communication are usually around 100 millivolts.

“Because we took the time to really dig in and understand the theoretical model behind this process, we can maximize the sensitivity of the antennas,” he says.

OCEANs also responded to changing signals in only a few milliseconds, enabling them to record electrical signals with fast kinetics. Moving forward, the researchers want to test the devices with real cell cultures. They also want to reshape the antennas so they can penetrate cell membranes, enabling more precise signal detection.

In addition, they want to study how OCEANs could be integrated into nanophotonic devices, which manipulate light at the nanoscale for next-generation sensors and optical devices.

This research is funded, in part, by the U.S. National Institutes of Health and the Swiss National Science Foundation.

The hippocampus plays a crucial role in memory formation, learning and emotional regulation. Hippocampal neuroinflammation occurs in a range of diseases and disorders such as Alzheimer’s, Multiple Sclerosis and Depression.

People with these diseases often experience common symptoms such as apathy, difficulty with daily activities and changes to food preferences. These symptoms also tend to be more severe in women than in men.

“While inflammation in the hippocampus is not solely responsible for behaviour changes, it likely triggers wider brain activity that influences behaviour,” said study co-author Dr Laura Bradfield, Director of the Brain and Behaviour Lab at the University of Technology Sydney (UTS).

“This research suggests that treatments targeting hippocampal neuroinflammation could help reduce cognitive and behavioural symptoms in these diseases and improve brain health, especially in women,” she said.

The study, “Hippocampal neuroinflammation induced by lipopolysaccharide causes sex-specific disruptions in action selection, food approach memories, and neuronal activation,” was published in the journal Brain Behavior and Immunity.

Researchers induced inflammation by exposing mouse hippocampal cell cultures in the lab to lipopolysaccharide, a bacterial toxin that elicits a strong immune response.

They found the toxin only activated neurons in the presence of other types of brain cells such as microglia and astrocytes. This highlights the complex interaction between different cell types during inflammation.

To examine behaviour, the researchers injected lipopolysaccharide directly into the hippocampus of mice and observed their activity and food-seeking behaviours.

They discovered that neuroinflammation increased movement and activity levels in both sexes but had a more pronounced effect on food-seeking behaviours in females.

Lead author Dr Kiruthika Ganesan, who recently completed her PhD at UTS, said the study underscores the importance of considering sex-specific effects when developing treatments for neurological diseases.

“These findings provide fresh insights into how neuroinflammation affects brain function, potentially paving the way for new therapies that address the behavioural and cognitive symptoms of a range of diseases,” she said.

“We hope that future research will focus on understanding the mechanisms behind these sex-specific effects, including the influence of hormones such as estrogen, and their implications for brain health.”

Published in Nature Cities, the study revealed the problem worsened following changes to the housing market triggered by the 2008 global crash. And since 2017 it has been “expanding in scope and severity” to affect a broader array of US cities including Portland (OR), Phoenix, Houston, Atlanta, Dallas-Fort Worth, and Philadelphia, as well as large urban areas such as Los Angeles, New York City and San Francisco.

The research also found that people of color were disproportionally affected by a lack of household water, a situation defined by the authors as ‘plumbing poverty’, in 12 of the 15 largest cities.

The researchers from King’s College London and the University of Arizona said the findings should “raise alarm bells” and warned it would take a “heroic” transformation of housing conditions and social infrastructures for the USA to meet the United Nations goal for everyone to have access to safe drinking water, sanitation and hygiene.

Lead researcher Professor Katie Meehan, Professor of Environmental Justice at King’s College London, UK, said: “It is alarming how many US cities, including those thought of as affluent and growing, are now home to more people living in situations of extreme poverty, namely without access to running water.

“Our research is the first effort to track these changes over time, starting in the 1970s and noting a dramatic urbanization of plumbing poverty in the 1990s and sharp acceleration triggered by the 2008 crash and the current housing and cost-of-living crisis.

“The compound pressures of high housing costs and expenditures mean that more low-income, asset-limited people are living without running water in these expensive cities. Far too many people, especially those of color, are now in such extreme poverty they are being pushed into homes that do not meet the basic standard for human dignity and life.”

Meehan said people can find themselves living without running water because of a range of reasons and, in most cases, people are working but not earning enough to make ends meet. Some households might have been disconnected from water service after falling behind with bills or had to “downgrade” to housing without any water access because other expenses take priority. Others might be in homes which have been poorly maintained by their landlord but cannot afford to move out, some might be living in buildings such as sheds or warehouses not designed to be homes, while others could be experiencing homelessness.

Lucy Everitt, a PhD student at King’s College London who was part of the research team, said water service shut-offs are a hidden problem across US cities that may be indirectly picked up by US census data.

“New York City tops the ‘worst offenders’ list for the total number of households in a US metro without running water. Despite this, the municipal Water Board issued more than 2,400 shutoff notices in March of this year alone to properties behind in their payments. Because our analysis tracks the status of running water in households, as measured by the US Census, we anticipate that we are capturing many thousands of households whose access is denied by their inability to pay.”

The study is the first to track the problem over a 51-year period in the 50 largest US cities. In the 1970s, according to census data, 3.5 million US households lacked running water and by 2021 this overall number had reduced, but 0.5 million households or 1.1million people still lacked household access to running water. This is equivalent to one out of 245 households live without running water. The team believe this is likely to be an underestimate of the true number because of limitations in US census data.

Other key findings from the study include:

• From 1990, plumbing poverty shifted from being a mainly rural to urban issue and latest figures show 71 percent of those in plumbing poverty now live in cities.
• In 2021, the New York City metro area led the nation in the number of people living in plumbing poverty — a staggering 56,900 people — followed by Los Angeles (45,900 people) and San Francisco (24,400 people).
• People of color represent the majority of individuals without access to running water in 12 of the 15 largest US cities, including Los Angeles (82%), Miami (79%), San Francisco (74%), and Houston (71%) in 2021.

Dr Jason R. Jurjevich, Assistant Professor in the School of Geography, Development and Environment at the University of Arizona who was part of the research team, said: “Our results underscore that the success in reducing plumbing poverty in select US cities over the past twenty years is uneven, with households of color often left behind. In Philadelphia, for example, people of color comprised 40% of the total population, but represented 66% of people without access to running water in 2021.”

The authors said not enough attention is being given to how the housing crisis is shaping people’s access to running water. They recommend reform and improvements to the US Census Bureau’s capacity to collect nationwide data about household water access and the extent of water service shut-offs, to monitor and meet SDG development goals. They also said local water utilities and water boards must revisit and overhaul low-income assistance programs in light of the expanding cost-of-living and housing expenses, which are ‘squeezing’ people’s ability to pay for water services.

The findings, published today in Nature Astronomy, reveal the distribution of ices in the early solar system and how TNOs evolve when they travel inward into the region of the giant planets between Jupiter and Saturn, becoming centaurs.

TNOs are small bodies, or ‘planetesimals,’ orbiting the sun beyond Pluto. They never accreted into planets, and serve as pristine time capsules, preserving crucial evidence of the molecular processes and planetary migrations that shaped the solar system billions of years ago. These solar system objects are like icy asteroids and have orbits comparable to or larger than Neptune’s orbit.

Prior to the new UCF-led study, TNOs were known to be a diverse population based on their orbital properties and surface colors, but the molecular composition of these objects remained poorly understood. For decades, this lack of detailed knowledge hindered interpretation of their color and dynamical diversity. Now, the new results unlock the long-standing question of the interpretation of color diversity by providing compositional information.

“With this new research, a more-complete picture of the diversity is presented and the pieces of the puzzle are starting to come together,” says Noemí Pinilla-Alonso, the study’s lead author.

“For the very first time, we have identified the specific molecules responsible for the remarkable diversity of spectra, colors and albedo observed in trans-Neptunian objects,” Pinilla-Alonso says. “These molecules — like water ice, carbon dioxide, methanol and complex organics — give us a direct connection between the spectral features of TNOs and their chemical compositions.”

Using the James Webb Space Telescope (JWST), the researchers found that TNOs can be categorized into three distinct compositional groups, shaped by ice retention lines that existed in the era when the solar system formed billions of years ago.

These lines are identified as regions where temperatures were cold enough for specific ices to form and survive within the protoplanetary disk. These regions, defined by their distance from the sun, mark key points in the early solar system’s temperature gradient and offer a direct link between the formation conditions of planetesimals and their present-day compositions.

Rosario Brunetto, the paper’s second author and a Centre National de la Recherche Scientifique researcher at the Institute d’Astrophysique Spatiale (Université Paris-Saclay), says the results are the first clear connection between formation of planetesimals in the protoplanetary disk and their later evolution. The work sheds light on how today’s observed spectral and dynamical distributions emerged in a planetary system that’s shaped by complex dynamical evolution, he says.

“The compositional groups of TNOs are not evenly distributed among objects with similar orbits,” Brunetto says. “For instance, cold classicals, which formed in the outermost regions of the protoplanetary disk, belong exclusively to a class dominated by methanol and complex organics. In contrast, TNOs on orbits linked to the Oort cloud, which originated closer to the giant planets, are all part of the spectral group characterized by water ice and silicates.”

Brittany Harvison, a UCF physics doctoral student who worked on the project while studying under Pinilla-Alonso, says the three groups defined by their surface compositions exhibit qualities hinting at the protoplanetary disk’s compositional structure.

“This supports our understanding of the available material that helped form outer solar system bodies such as the gas giants and their moons or Pluto and the other inhabitants of the trans-Neptunian region,” she says.

In a complementary study of centaurs published in the same volume of Nature Astronomy, the researchers found unique spectral signatures, different from TNOs, that reveal the presence of dusty regolith mantles on their surfaces.

This finding about centaurs, which are TNOs that have shifted their orbits into the region of the giant planets after a close gravitational encounter with Neptune, helps illuminate how TNOs become centaurs as they warm up when getting closer to the sun and sometimes develop comet-like tails.

Their work revealed that all observed centaur surfaces showed special characteristics when compared with the surfaces of TNOs, suggesting modifications occurred as a consequence of their journey into the inner solar system.

Among the three classes of TNO surface types, two — Bowl and Cliff — were observed in the centaur population, both of which are poor in volatile ices, Pinilla-Alonso says.

However, in centaurs, these surfaces show a distinguishing feature: they are covered by a layer of dusty regolith intermixed with the ice, she says.

“Intriguingly, we identify a new surface class, nonexistent among TNOs, resembling ice poor surfaces in the inner solar system, cometary nuclei and active asteroids,” she says.

Javier Licandro, senior researcher at the Instituto de Astrofisica de Canarias (IAC, Tenerife, Spain) and lead author of the centaur’s work says the spectral diversity observed in centaurs is broader than expected, suggesting that existing models of their thermal and chemical evolution may need refinement.

For instance, the variety of organic signatures and the degree of irradiation effects observed were not fully anticipated, Licandro says.

“The diversity detected in the centaurs populations in terms of water, dust, and complex organics suggests varied origins in the TNO population and different evolutionary stages, highlighting that centaurs are not a homogenous group but rather dynamic and transitional objects” Licandro says. “The effects of thermal evolution observed in the surface composition of centaurs are key to establishing the relationship between TNOs and other small bodies populations, such as the irregular satellites of the giant planets and their Trojan asteroids.”

Study co-author Charles Schambeau, a planetary scientist with UCF’s Florida Space Institute (FSI) who specializes in studying centaurs and comets, emphasized the importance of the observations and that some centaurs can be classified into the same categories as the DiSCo-observed TNOs.

“This is pretty profound because when a TNO transitions into a centaur, it experiences a warmer environment where surface ices and materials are changed,” Schambeau says. “Apparently, though, in some cases the surface changes are minimal, allowing individual centaurs to be linked to their parent TNO population. The TNO versus centaur spectral types are different, but similar enough to be linked.”

How the Research Was Performed

The studies are part of the Discovering the Surface Composition of the trans-Neptunian Objects, (DiSCo) project, led by Pinilla-Alonso, to uncover the molecular composition of TNOs. Pinilla-Alonso is now a distinguished professor with the Institute of Space Science and Technology in Asturias at the Universidad de Oviedo and performed the work as a planetary scientist with FSI.

For the studies, the researchers used the JWST, launched almost three years ago, that provided unprecedented views of the molecular diversity of the surfaces of the TNOs and centaurs through near-infrared observations, overcoming the limitations of terrestrial observations and other available instruments.

For the TNOs study, the researchers measured the spectra of 54 TNOs using the JWST, capturing detailed light patterns of these objects. By analyzing these high-sensitivity spectra, the researchers could identify specific molecules on their surface. Using clustering techniques, the TNOs were categorized into three distinct groups based on their surface compositions. The groups were nicknamed “Bowl,” “Double-dip” and “Cliff” due to the shapes of their light absorption patterns.

They found that:

• Bowl-type TNOs made up 25% of the sample and were characterized by strong water ice absorptions and a dusty surface. They showed clear signs of crystalline water ice and had low reflectivity, indicating the presence of dark, refractory materials.

• Double-dip TNOs accounted for 43% of the sample and showed strong carbon dioxide (CO2) bands and some signs of complex organics.

• Cliff-type TNOs made up 32% of the sample and had strong signs of complex organics, methanol, and nitrogen-bearing molecules, and were the reddest in color.

For the centaurs study, the researchers observed and analyzed the reflectance spectra of five centaurs (52872 Okyrhoe, 3253226 Thereus, 136204, 250112 and 310071). This allowed them to identify the surface compositions of the centaurs, revealing considerable diversity among the observed sample.

They found that Thereus and 2003 WL7 belong to the Bowl-type, while 2002 KY14 belongs to the Cliff-type. The remaining two centaurs, Okyrhoe and 2010 KR59, did not fit into any existing spectral classes and were categorized as “Shallow-type” due to their unique spectra. This newly defined group is characterized by a high concentration of primitive, comet-like dust and little to no volatile ices.

Previous Research and Next Steps

Pinilla-Alonso says that previous DiSCo research revealed the presence of carbon oxides widespread on the surfaces of TNOs, which was a significant discovery.

“Now, we build on that finding by offering a more comprehensive understanding of TNO surfaces” she says. “One of the big realizations is that water ice, previously thought to be the most abundant surface ice, is not as prevalent as we once assumed. Instead, carbon dioxide (CO₂) — a gas at Earth’s temperature — and other carbon oxides, such as the super volatile carbon monoxide (CO), are found in a larger number of bodies.”

The new study’s findings are only the beginning, Harvison says.

“Now that we have general information about the identified compositional groups, we have much more to explore and discover,” she says. “As a community, we can start exploring the specifics of what produced the groups as we see them today.”

The research was supported by NASA through a grant from the Space Telescope Science Institute.