Posts tagged with "rice university"

Neurological illustration by Heather Skovlund for 360 Magazine

Houston Methodist × Rice University

Houston Methodist, Rice U. launch neuroprosthetic collaboration


Center for Translational Neural Prosthetics and Interfaces to focus on restoring brain function after disease, injury

Neurosurgery’s history of cutting diseases out of the brain is morphing into a future in which implanting technology intothe brain may help restore function, movement, cognition and memory after patients suffer strokes, spinal cord injuries and other neurological disorders. Rice University and Houston Methodist have forged a partnership to launch the Center for Translational Neural Prosthetics and Interfaces, a collaboration that brings together scientists, clinicians, engineers and surgeons to solve clinical problems with neurorobotics.  

“This will be an accelerator for discovery,” said center co-director Dr. Gavin Britz, chair of the Houston Methodist Department of Neurosurgery. “This center will be a human laboratory where all of us — neurosurgeons, neuroengineers, neurobiologists — can work together to solve biomedical problems in the brain and spinal cord. And it’s a collaboration that can finally offer some hope and options for the millions of people worldwide who suffer from brain diseases and injuries.”

Houston Methodist neurosurgeons, seven engineers from the Rice Neuroengineering Initiative and additional physicians and faculty from both institutions form the center’s core team. The center also plans to hire three additional engineers who will have joint appointments at Houston Methodist and Rice. Key focus areas include spinal cord injury, memory and epilepsy studies, and cortical motor/sensation conditions.

“The Rice Neuroengineering Initiative was formed with this type of partnership in mind,” said center co-director Behnaam Aazhang, Rice’s J.S. Abercrombie Professor of Electrical and Computer Engineering, who also directs the neuroengineering initiative, which launched in 2019 to bring together the brightest minds in neuroscience, engineering and related fields to improve lives by restoring and extending the capabilities of the human brain. “Several core members, myself included, have existing collaborations with our colleagues at Houston Methodist in the area of neural prosthetics. The creation of the Center for Translational Neural Prosthetics and Interfaces is an exciting development toward achieving our common goals.”

The physical space for the center’s operation includes more than 25,000 square feet of Rice Neuroengineering Initiative laboratories and experimental spaces in the university’s BioScience Research Collaborative, as well as an extensive build-out underway at Houston Methodist’s West Pavilion location that’s expected to be completed late this year. The Houston Methodist facility will include operating rooms and a human laboratory where ongoing patient/volunteer diagnosis and assessment, device fabrication and testing, and education and training opportunities are planned.

“This partnership is a perfect blend of talent,” said Rice’s Marcia O’Malley, a core member of both the new center and university initiative and the Thomas Michael Panos Family Professor in Mechanical Engineering. “We will be able to design studies to test the efficacy of inventions and therapies and rely on patients and volunteers who want to help us test our ideas. The possibilities are limitless.”

Houston Methodist neurobiologist Philip Horner describes the lab as “a merging of wetware with hardware,” where robotics, computers, electronic arrays and other technology — the hardware — is incorporated into the human brain or spinal cord — the wetware. The centerpiece of this working laboratory is a zero-gravity harness connected to a walking track, with cameras and sensors to record feedback, brain activity and other data.

While the Houston Methodist space is being built, collaborations already are underway between the two institutions, which sit across Main Street from one another in the Texas Medical Center. Among them are the following:

  • O’Malley and Houston Methodist’s Dr. Dimitry Sayenko, assistant professor of neurosurgery, will head the first pilot project involving the merging of two technologies to restore hand function following a spinal cord injury or stroke. O’Malley will pair the upper limb exoskeleton she invented with Sayenko’s noninvasive stimulator designed to wake up the spinal cord. Together, they hope these technologies will help patients achieve a more extensive recovery — and at a faster pace.
  • Rice neuroengineer Lan Luan, assistant professor of electrical and computer engineering, and Britz, a neurosurgeon, are collaborating on a study to measure the neurovascular response following a subarachnoid hemorrhage, a life-threatening stroke caused by bleeding just outside the brain. Two-thirds of people who suffer these brain bleeds either die or end up with permanent disabilities. Luan invented very small and flexible electrodes that can be implanted in the brain to measure, record and map its activities. Her work with mice could lead to human brain implants that may help patients recover from traumatic brain injuries caused by disease or accidents.
  • Aazhang, Britz and Taiyun Chi, assistant professor of electrical and computer engineering at Rice, are collaborating on the detection of mild traumatic brain injuries (mTBI) from multimodal observations and on alleviating mTBI using neuromodulations. This project is of particular interest to the Department of Defense.
Green covid by Mina Tocalini for 360 Magazine

Tuberculosis Bacteria Paradox

TB-causing bacteria remember prior stress, react quickly to new stress

Tuberculosis bacteria have evolved to remember stressful encounters and react quickly to future stress, according to a study by computational bioengineers at Rice University and infectious disease experts at Rutgers New Jersey Medical School (NJMS).

Published online in the open-access journal mSystems, the research identifies a genetic mechanism that allows the TB-causing bacterium, Mycobacterium tuberculosis, to respond to stress rapidly and in manner that is “history-dependent,” said corresponding author Oleg Igoshin, a professor of bioengineering at Rice.

Researchers have long suspected that the ability of TB bacteria to remain dormant, sometimes for decades, stems from their ability to behave based upon past experience.

Latent TB is an enormous global problem. While TB kills about 1.5 million people each year, the World Health Organization estimates that 2-3 billion people are infected with a dormant form of the TB bacterium.

“There’s some sort of peace treaty between the immune system and bacteria,” Igoshin said. “The bacteria don’t grow, and the immune system doesn’t kill them. But if people get immunocompromised due to malnutrition or AIDS, the bacteria can be reactivated.”

One of the most likely candidates for a genetic switch that can toggle TB bacteria into a dormant state is a regulatory network that is activated by the stress caused by immune cell attacks. The network responds by activating several dozen genes the bacteria use to survive the stress. Based on a Rice computational model, Igoshin and his longtime Rutgers NJMS collaborator Maria Laura Gennaro and colleagues predicted just such a switch in 2010. According to the theory, the switch contained an ultrasensitive control mechanism that worked in combination with multiple feedback loops to allow hysteresis, or history-dependent behavior.

“The idea is that if we expose cells to intermediate values of stress, starting from their happy state, they don’t have that much of a response,” Igoshin explained. “But if you stress them enough to stop their growth, and then reduce the stress level back to an intermediate level, they remain stressed. And even if you fully remove the stress, the gene expression pathway stays active, maintaining a base level of activity in case the stress comes back.”

In later experiments, Gennaro’s team found no evidence of the predicted control mechanism in Mycobacterium smegmatis, a close relative of the TB bacterium. Since both organisms use the same regulatory network, it looked like the prediction was wrong. Finding out why took years of follow-up studies. Gennaro and Igoshin’s teams found that the TB bacterium, unlike their noninfectious cousins, had the hysteresis control mechanism, but it didn’t behave as expected.

“Hysteretic switches are known to be very slow, and this wasn’t,” Igoshin said. “There was hysteresis, a history-dependent response, to intermediate levels of stress. But when stress went from low to high or from high to low, the response was relatively fast. For this paper, we were trying to understand these somewhat contradictory results. ”

Igoshin and study co-author Satyajit Rao, a Rice doctoral student who graduated last year, revisited the 2010 model and considered how it might be modified to explain the paradox. Studies within the past decade had found a protein called DnaK played a role in activating the stress-response network. Based on what was known about DnaK, Igoshin and Rao added it to their model of the dormant-active switch.

“We didn’t discover it, but we proposed a particular mechanism for it that could explain the rapid, history-dependent switching we’d observed,” Igoshin said. “What happens is, when cells are stressed, their membranes get damaged, and they start accumulating unfolded proteins. Those unfolded proteins start competing for DnaK.”

DnaK was known to play the role of chaperone in helping rid cells of unfolded proteins, but it plays an additional role in the stress-response network by keeping its sensor protein in an inactive state.

“When there are too many unfolded proteins, DnaK has to let go of the sensor protein, which is an activation input for our network,” Igoshin said. “So once there are enough unfolded proteins to ‘distract’ DnaK, the organism responds to the stress.”

Gennaro and co-author Pratik Datta conducted experiments at NJMS to confirm DnaK behaved as predicted. But Igoshin said it is not clear how the findings might impact TB treatment or control strategies. For example, the switch responds to short-term biochemical changes inside the cell, and it’s unclear what connection, if any, it may have with long-term behaviors like TB latency, he said.

“The immediate first step is to really try and see whether this hysteresis is important during the infection,” Igoshin said. “Is it just a peculiar thing we see in our experiments, or is it really important for patient outcomes? Given that it is not seen in the noninfectious cousin of the TB bacterium, it is tempting to speculate it is related to survival inside the host.”

Gennaro is a professor of medicine and epidemiology at Rutgers Biomedical and Health Sciences. Igoshin is a senior investigator at Rice’s Center for Theoretical Biological Physics.

The research was supported by the Welch Foundation (C-1995) and the National Institutes of Health (GM096189, AI122309, AI104615, HL149450).

New Scientific Study by Rice University Biochemists

Michael Stern and James McNew (Photo by Jeff Fitlow/Rice University)

Study: Early, late stages of degenerative diseases are distinct
Two-phase theory applies to diseases like Alzheimer’s, Parkinson’s, muscle atrophy

Rice University biochemists Michael Stern and James McNew have studied how neurodegeneration kills cells. They’ve conducted countless experiments over more than a decade, and they’ve summarized all they’ve learned in a simple diagram they hope may change how doctors perceive and treat degenerative diseases as varied as Alzheimer’s, Parkinson’s, and muscle atrophy.

In a study published this month in Molecular Psychiatry, McNew and Stern propose that degeneration, at the cellular level, occurs in two distinct phases that are marked by very different activities of protein signaling pathways that regulate basic cell functions.

“We would like clinicians and other researchers to understand that the two phases of degeneration represent distinct entities, with distinct alterations in signaling pathways that have distinct effects on disease pathology,” said Stern, a professor of biosciences at Rice. “In other words, we think that patients need to be treated differently depending on which phase they are in.”

Stern and McNew’s diagram shows how the activity of key cell-signaling proteins either increases or decreases at the onset of degeneration, ultimately bringing about oxidative stress. Oxidative stress then brings about the second phase of the condition, during which degeneration occurs, where the signaling proteins implicated in the first phase behave in a completely different way.

Because cells behave quite differently in the two phases, the research suggests patients in different phases of a disease may respond differently to the same treatment.

“The two phases of degeneration haven’t been previously recognized, so it hasn’t been understood, clinically, that you have two different populations of patients,” McNew said. “Today, they’re treated like one population, and we think this has confounded clinical trials and explains why some trials on Alzheimer’s have given variable and irreproducible effects. It would be like trying to treat all meningitis patients with antibiotics without realizing that there are two types of meningitis, one bacterial and one viral.”

Stern and McNew, professors of biochemistry and cell biology in Rice’s Department of BioSciences, became interested in the cellular processes of neurodegenerative disorders when they began studying hereditary spastic paraplegia (HSP) in the late 2000s. A rare disorder, HSP is marked by numbness and weakness in the legs and feet due to the progressive deterioration of neurons that connect the spine and lower leg.

These are some of the longest cells in the body, and starting with clues about structural defects that could cause them to degenerate, McNew and Stern used experiments on fruit flies to systematically piece together the biochemical domino effect that caused the neurons to progressively lose more and more function and eventually die. It had been thought that nerve damage could lead to muscle atrophy, but their studies found that muscle cells attached to the neurons started degenerating from the same type of biochemical cascade before the nerve cells died.

A key player in the cascade was a protein called TOR, a master regulator of cell growth and an essential protein for all higher-order life from yeast to humans. TOR acts like a knob, dialing growth up or down to suit the conditions a cell is experiencing. In some conditions, high growth is warranted and beneficial, and in other situations, growth needs to be dialed back so energy and resources can be conserved for daily chores, like the recycling or repair that take place during a process known as autophagy.

Some cancers highjack TOR to promote aggressive cell growth, and increased TOR activity has also been implicated in neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases and in diseases marked by muscle atrophy. After compiling evidence about how TOR and several other signaling proteins behaved in neurodegeneration, McNew and Stern won a grant from the National Institute of Neurological Disorders and Stroke in 2018 for experiments to investigate signaling pathway changes that occur in the early stages of degeneration.

“At the time, we thought there might be a late phase during which degeneration actually occurs, but we didn’t propose any experiments to test that,” Stern said. “In the new paper, we’re explicit about the existence of a late phase. We propose mechanistically why degeneration occurs only during this phase, and cite abundant research in support.”

Stern said the two-phase process described in the study “is the basic engine that drives most or even all forms of degeneration forward. However, in addition, there are also inputs whose role is to specify how fast the engine turns over.”

To understand neurodegeneration, it’s critical to understand how those inputs work, he said. For example, insulin resistance plays a well-known role in driving Alzheimer’s disease, and in the study, McNew and Stern describe how it does that by accelerating progression through the early phase.

“Similarly, our data suggests that decreases in synaptic transmission, as occurs in our HSP insect model, likewise triggers degeneration by accelerating progression through the early phase,” McNew said. “Our NIH grant was funded so that we could learn the mechanism by which that occurs.”

Now that they clearly understand that two phases of degeneration exist, Stern said he and McNew would like to carry out more experiments to see how the effects of specific genes on degeneration are altered when they are activated in the early and late phases.

“What we would like to do in the last two years of the grant is to obtain data to test some of the predictions we have made, which will help determine if the ideas we have presented are likely to be correct,” Stern said.

The research was supported by the National Institutes of Health (R01-NS102676).

Mina Tocalini, 360 Magazine, COVID-19

New Possible Key for Targeting Viruses

“Position 4” didn’t seem important until researchers took a long look at a particular peptide. That part of the peptide drawn from a SARS-CoV virus turned out to have an unexpected but significant influence on how it stably binds with a receptor central to the immune system’s ability to attack diseased cells. 

In a study published by the Proceedings of the National Academy of Sciences, researchers at Rice University’s Brown School of Engineering and the University of Texas MD Anderson Cancer Center revealed models at an atomic resolution that detail not only the binding but also, for the first time, the unbinding mechanisms that underlie a key component of the immune system. 

They say a better understanding of the entire mechanism could lead to advancements in immunotherapy that boost the body’s ability to fight disease. 

Rice computer scientist Lydia Kavraki, alumnus Jayvee Abella and postdoctoral researcher Dinler Antunes, led the study.

“Finding good targets to trigger a protective immune response is very challenging, especially in cancer research,” Antunes said. “The fact that this particular peptide was predicted not to bind to HLAs (human leukocyte antigens) by sequence-based methods highlights a blind spot in our current prediction capacity.”

“By incorporating structural analysis, we can detect the contribution of these secondary interactions to peptide binding and stability, hopefully enabling us to find better targets for antiviral vaccine development and T-cell-based cancer immunotherapy,” he said.

The researchers used their simulations to illuminate details of how the intracellular SARS peptide, QFKDNVILL, binds to an MHC receptor protein known as HLA-A24:02, primarily at dominant anchors on both ends of the peptide (at positions 2 and 9) and presents them for inspection to the immune system’s T cells. 

Stable binding of a peptide and MHC is a prerequisite to the activation of T cells, which look for peptides not normally found in healthy cells. If the peptide and protein don’t bind, the T cell is not prompted to attack. 

“That much was known from previous studies of the bound and unbound states of many such complexes,” Kavraki said. “What they didn’t capture was the intermediate states and the transitions that lead from one state to another, especially the unbinding.

“I think this is the only analysis that shows the unbinding of peptides from the MHC with atomic resolution,” Kavraki said. “Other peptides have similar characteristics and we think they would have similar behaviors.”

All of these interactions were revealed in great detail through Markov state models that analyze how systems change over time. In this case, the models revealed the importance of secondary sites that support the peptide’s primary anchors. That’s where position 4 stood out.

“There are the main, canonical anchors that people know, but there are these secondary interactions that contribute to the binding and the stability,” Antunes said. “These are harder to capture, but in this study, it seems that position 4 plays a very important role. When you mutate it, it affects the behavior of the peptide as it unbinds from the molecule.”

The researchers modeled mutations of the MHC to see how they would influence binding and found they supported the importance of position 4 to the stability of the complex.

“Our computational approach was able to make predictions on the effect of mutations that are then experimentally verified,” said co-author Cecilia Clementi, a former Rice professor who recently became Einstein Professor of Physics at the Free University of Berlin. 

The researchers developed a two-stage process to simplify the computational complexity of atom-scale analysis of large molecules. The first stage used a technique called umbrella sampling to accelerate the initial exploration of the molecules. The second, exploratory stage used adaptive sampling, in which simulations are driven to accelerate the construction of the Markov model.  

“The challenge is that these MHCs are pretty large systems for computational chemists to simulate,” said Abella, whose research on the topic formed much of his doctoral thesis. “We had to make some approximations and leverage advances in these classes of methods to move forward.”

“We’re not the first one to study unbinding, but what characterizes our work over others is that we keep full atomic resolution in our simulations,” he said. “Other works use a technique known as a Markov chain Monte Carlo, whereas we use molecular dynamics, which lets us incorporate time into our computation to capture the kinetics.”

Their methods can be applied to other peptide-MHC complexes with existing 3D models. “This was, in some sense, a feasibility study to show we can use molecular dynamics and build a Markov state model of a system this size,” Abella said. 

The researchers also noted the study’s relevance to the current fight against COVID-19, as the SARS peptide they viewed, QFKDNVILL, is highly similar to the NFKDQVILL peptide in SARS-CoV-2, with the same binding pockets in positions 2, 4 and 9.

“These results suggest that both peptides can bind to HLA-A*2402 and provide targets for anti-viral T-cell responses, which are of great interest in light of the current pandemic,” said co-author Gregory Lizée, a professor in the Department of Melanoma Medical Oncology at MD Anderson. “But these results also shed light on many other potential immune targets, including those of other viruses and even human cancers.”

Kavraki noted that experimental work by long-term collaborator Lizée and Kyle Jackson, a graduate research assistant at Lizée’s lab who produced the mutant proteins, were critical to validate their simulations. Kavraki’s own lab won a National Science Foundation (NSF) Rapid Response Research grant to help identify fragments of SARS-CoV-2 viral proteins as possible targets for vaccine development. 

Kavraki is the Noah Harding Professor of Computer Science and a professor of bioengineering, mechanical engineering and electrical and computer engineering. 

The Cancer Prevention and Research Institute of Texas, the Gulf Coast Consortia, the NSF, the Einstein Foundation Berlin and the Welch Foundation supported the research.

Loose Standards Undermined Research on COVID-19 Test Accuracy

The COVID-19 pandemic was met with a rush of research on the many factors related to the crisis, including the accuracy of different testing methods. However, many of the studies conducted in the early stages of the pandemic did not meet the usual rigorous scientific standards, according to researchers at Rice University and Baylor College of Medicine.

In “The estimation of diagnostic accuracy of tests for COVID-19: A scoping review,” which will appear in an upcoming edition of the Journal of Infection, authors Dierdre Axell-House, Richa Lavingia, Megan Rafferty, Eva Clark, E. Susan Amirian and Elizabeth Chiao found that better-designed studies are needed to appropriately evaluate the different types of COVID-19 tests.

They reviewed 49 articles published between Dec. 31, 2019, and June 19, 2020, that evaluated the validity of different types of coronavirus testing. These studies were assessed using elements of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines, which are used to evaluate if bias could be playing a role in the results of studies on diagnostic test accuracy.

Amirian, an epidemiologist at Rice’s Texas Policy Lab (TPL), said when it comes to conducting studies on testing accuracy, design is critically important. She said the major limitations found in the design of most of the studies they examined could lead to erroneous or misleading results.

“Without rigorous evaluations of which tests are the most accurate, it’s hard to know which tests are more likely to lead to false negatives, which could contribute to greater spread of the virus,” said Rafferty, a health data analyst at the TPL. “Although it’s difficult to say, some of the quality issues may have resulted from these studies being streamlined in response to the immediate need for timely information.”

“COVID-19 has now been a health crisis for nearly a year,” Amirian said. “With regard to research, the academic community needs to move away from being in acute emergency mode and think about how we’re going to handle this as a chronic crisis. When researchers are in emergency mode, we tend to be more open to sacrificing a lot of the strict quality standards for conducting research that we usually uphold.”

The paper is available online here.

A Trillion Turns of Light Nets Terahertz Polarized Bytes

American and Italian engineers have demonstrated the first nanophotonic platform capable of manipulating polarized light 1 trillion times per second. 

“Polarized light can be used to encode bits of information, and we’ve shown it’s possible to modulate such light at terahertz frequencies,” said Rice University’s Alessandro Alabastri, co-corresponding author of a study published this week in Nature Photonics.

 “This could potentially be used in wireless communications,” said Alabastri, who is also an assistant professor of electrical and computer engineering in Rice’s Brown School of Engineering. “The higher the operating frequency of a signal, the faster it can transmit data. One terahertz equals 1,000 gigahertz, which is about 25 times higher than the operating frequencies of commercially available optical polarization switches.”

This new found research was a collaboration between experimental and theoretical teams at Rice, the Polytechnic University of Milan and the Italian Institute of Technology in Genoa. This collaboration started in the summer of 2017 when co-author of the study, Andrea Schirato was a visiting scholar in the Rice lab of physicists along with co-author Peter Nordlander. Schirato is a Politecnico-IIT joint graduate student under the supervision of co-corresponding author Giuseppe Della Valle and co-author Remo Proietti Zaccaria. 

Each of the researchers work in nanophotonics, a fast-growing field that uses ultrasmall, engineered structures to manipulate light. Their idea for ultrafast polarization control was to capitalize on tiny, fleeting variations in the generation of high-energy electrons in a plasmonic metasurface.

 Metasurfaces are ultrathin films or sheets that contain embedded nanoparticles that interact with light as it passes through the film. By varying the size, shape and makeup of the embedded nanoparticles and by arranging them in precise two-dimensional geometric patterns, engineers can craft metasurfaces that split or redirect specific wavelengths of light with precision.

“One thing that differentiates this from other approaches is our reliance on an intrinsically ultrafast broadband mechanism that’s taking place in the plasmonic nanoparticles,” Alabastri said. 

The Rice-Politecnico-IIT team designed a metasurface that contained rows of cross-shaped gold nanoparticles. Each plasmonic cross was about 100 nanometers wide and resonated with a specific frequency of light that gave rise to an enhanced localized electromagnetic field. Thanks to this plasmonic effect, the team’s metasurface was a platform for generating high-energy electrons.

“When one laser light pulse hits a plasmonic nanoparticle, it excites the free electrons within it, raising some to high-energy levels that are out of equilibrium,” Schirato said. “That means the electrons are ‘uncomfortable’ and eager to return to a more relaxed state. They return to an equilibrium in a very short time, less than one picosecond.”

Experiments were performed by study co-first author Margherita Maiuri at Politecnico’s ultrafast spectroscopy laboratories and they were confirmed by the team’s theoretical predictions. She used an ultrashort pulse of light from one laser to excite the crosses, allowing them to modulate the polarization of light in a second pulse that arrived less than a picosecond after the first.

Despite the symmetric arrangement of crosses in the metasurface, the nonequilibrium state has asymmetric properties that disappear when the system returns to equilibrium. To exploit this ultrafast phenomenon for polarization control, the researchers used a two-laser setup.

“The key point is that we could achieve the control of light with light itself, exploiting ultrafast electronic mechanisms peculiar of plasmonic metasurfaces,” Alabastri said. “By properly designing our nanostructures, we have demonstrated a novel approach that will potentially allow us to optically transmit broadband information encoded in the polarization of light with unprecedented speed.”

Bisexual adults less likely to enjoy health benefits of education

Education has long been linked to health — the more schooling people have, the healthier they are likely to be. But a new study from Rice University sociologists found that the health benefits of a good education are less evident among well-educated bisexual adults.

“Education and health: The joint role of gender and sexual identity” examines health among straight, bisexual, gay and lesbian adults with various educational backgrounds. Authors Zhe Zhang, a postdoctoral research fellow at Rice, Bridget Gorman, a professor of sociology at Rice, and Alexa Solazzo, a postdoctoral research fellow at the Harvard University T.H. Chan School of Public Health, were particularly interested in bisexual adults, since they may experience distinctive health vulnerabilities.

The researchers found that while having at least a bachelor’s degree was linked to better health among bisexual adults, they received less benefit than heterosexual and gay or lesbian adults with similar education. This effect was especially true for bisexual women.

“The health benefits of education are well established — so much so that anything we do to promote and improve public education should really be viewed as health policy,” Gorman said. “It’s that impactful on health and well-being. That our analysis showed less health benefit associated with education among bisexual adults compared to heterosexual, gay and lesbian adults is concerning.”

While the researchers could not pinpoint the exact cause, they theorized the problem might be social stigma and additional anxiety among women due to gender discrimination, Zhang said.

“Discrimination of any kind can take a heavy toll on health,” Zhang said. “While we cannot say with certainty that is what is happening in this study, it’s a very real possibility.”

The authors based their study on data from the Behavioral Risk Factor Surveillance System, which included a sample of more than 1.2 million adults living in 44 U.S. states and territories from 2011-2017. They hope the study will raise awareness of the issue and help health professionals provide better care.

The research was partially supported by a grant from the National Cancer Institute. The article is available online at https://bit.ly/3iJdNY0 and it will be published in the December 2020 edition of the journal SSM-Population Health.

This news release can be found online at news.rice.edu.

Follow Rice News and Media Relations on Twitter @RiceUNews.

Musicians x Social Distancing

Engineers and musicians from Rice University’s Shepherd School of Music and the Houston Symphony determined social distancing will not be enough to keep musicians safe while performing on-stage.

Using a high-speed camera, researchers studied air released by musicians who were singing or playing wind instruments.

Ashok Veeraraghavan, a Rice imaging expert, said social distancing is important, but other factors must be taken into account.

“Our main message is that there is no single silver bullet. Performance venues are going to need a mix of several different risk mitigation strategies. Each of them will help a little, and the sum total of all of them will minimize risk to both the performers and the audience,” Veeraraghavan said.

Robert Yekovich, dean of the Shepherd School of Music and co-principal investigator of the study, said a goal of the study was to help people return to the stage, which is why the findings are being published.

“Peer review may take a year or more, and we believe it is imperative to make others aware of what we found,” Yekovich said.

Schlieren imaging is a method used to study airflow, so Yekovich, Veeraraghavan and John Mangum, the president and CEO of the Houston Symphony, used it to study singers and flute, oboe, clarinet, bassoon, horn, trombone, trumpet and tuba players.

With cameras, a high-resolution background and computational algorithms, they were able to see and track air flow after it leaves mouths and instruments and travels throughout the room.

While the travel of large droplets is well-documented, they wanted to study microdroplets, which can linger in the air for hours.

The group hypothesized that the microdroplets would be the most important droplets to pay attention to. The experiment showed that exhaled air and droplets tended to rise to the top of the room.

“Because exhaled air was warmer than the room air, we found most of it rose rather quickly, carrying the bulk of exhaled microdroplets into air currents that were primarily driven by ventilation,” Veeraraghavan said.

They now recommend music venues meeting or exceeding federal guidelines of six room air exchanges per hour. They also suggest that venues themselves consider air filtration above the stage.

Veeraraghavan still said social distancing is important because of the large droplets, adding that masks should be worn.

Mangum thought that social distancing would be the most important thing when welcoming performers and audiences back to venues, but it’s going to take a bit more than standing six feet apart.

“The Rice experiments showed it’s more complex than that. Now we want all musical organizations and individual musicians to benefit from that understanding,” Mangum said.

You can see the results of the study by clicking right here. A video is also available by clicking right here.

Heart Attack Damage Reduced by Shielded Stem Cells

Bioengineers and surgeons from Rice University and Baylor College of Medicine (BCM) have shown that shielding stem cells with a novel biomaterial improves the cells’ ability to heal heart injuries caused by heart attacks.

In a study using rodents, a team led by Rice’s Omid Veiseh and Baylor’s Ravi Ghanta showed it could make capsules of wound-healing mesenchymal stem cells (MSCs) and implant them next to wounded hearts using minimally invasive techniques. Within four weeks, heart healing was 2.5 times greater in animals treated with shielded stem cells than those treated with nonshielded stem cells.

The study is available online in the Royal Society of Chemistry journal Biomaterials Science.

Someone has a heart attack every 40 seconds in the United States. In each case, an artery that supplies blood to the heart becomes blocked and heart muscle tissue dies due to lack of blood. Hearts damaged by heart attacks pump less efficiently, and scar tissue from heart attack wounds can further reduce heart function.

“What we’re trying to do is produce enough wound-healing chemicals called reparative factors at these sites so that damaged tissue is repaired and restored, as healthy tissue, and dead tissue scars don’t form,” said Veiseh, an assistant professor of bioengineering and CPRIT Scholar in Cancer Research at Rice.

Ghanta, associate professor of surgery at Baylor, a cardiothoracic surgeon at Harris Health’s Ben Taub Hospital and co-lead author of the study, said prior studies have shown that MSCs, a type of adult stem cell produced in blood marrow, can promote tissue repair after a heart attack. But in clinical trials of MSCs, “cell viability has been a consistent challenge,” Ghanta said.

“Many of the cells die after transplantation,” he said. “Initially, researchers had hoped that stem cells would become heart cells, but that has not appeared to be the case. Rather, the cells release healing factors that enable repair and reduce the extent of the injury. By utilizing this shielded therapy approach, we aimed to improve this benefit by keeping them alive longer and in greater numbers.”

A few MSC lines have been approved for human use, but Veiseh said transplant rejection has contributed to their lack of viability in trials.

“They’re allogenic, meaning that they’re not from the same recipient,” he said. “The immune system perceives them as foreign. And so very rapidly, the immune system starts chewing at them and clearing them out.”

Veiseh has spent years developing encapsulation technologies that are specifically designed not to activate the body’s immune system. He co-founded Sigilon Therapeutics, a Cambridge, Massachusetts-based biotech company that is developing encapsulated cell therapeutics for chronic diseases. Trials of Sigilon’s treatment for hemophilia A are expected to enter the clinic later this year.

“The immune system doesn’t recognize our hydrogels as foreign, and doesn’t initiate a reaction against the hydrogel,” Veiseh said. “So we can load MSCs within these hydrogels, and the MSCs live well in the hydrogels. They also secrete the same reparative factors that they normally do, and because the hydrogels are porous, the wound-healing factors just diffuse out.”

In previous studies, Veiseh and colleagues have shown that similar capsules can keep insulin-producing islet cells alive and thriving in rodents for more than six months. In the heart study, study co-lead author Samira Aghlara-Fotovat, a Rice bioengineering graduate student in Veiseh’s lab, created 1.5-millimeter capsules that each contained about 30,000 MSCs. Several of the capsules were placed alongside wounded sections of heart muscle in animals that had experienced a heart attack. The study compared rates of heart healing in animals treated with shielded and unshielded stem cells, as well as an untreated control group.

“We can deliver the capsules through a catheter port system, and that’s how we imagine they would be administered in a human patient,” Veiseh said. “You could insert a catheter to the area outside of the heart and inject through the catheter using minimally invasive, image-guided techniques.”

Veiseh said capsules in the study were held in place by the pericardium, a membrane that sheaths the heart. Tests at two weeks showed that MSCs were alive and thriving inside the implanted spheres.

More than 800,000 Americans have hearts attacks each year, and Ghanta is hopeful that encapsulated MSCs can one day be used to treat some of them.

“With further development, this combination of biomaterials and stem cells could be useful in delivering reparative therapy to heart attack patients,” he said.

“The pathway to regulatory approval could be streamlined as well,” said Veiseh.

“Clinical grade, allogenic MSCs are commercially available and are actively being used in patients for a range of applications,” he said.

Veiseh credited Aghlara-Fotovat with doing much of the work on the project.

“She basically executed the vision,” he said. “She developed the hydrogel formulation, the concept of how to package the MSCs within the hydrogel, and she did all the in vitro validation work to show that MSCs remained viable in the capsules.”

Aghlara-Fotovat is co-mentored by Ghanta and worked in his lab at Baylor alongside research assistant Aarthi Pugazenthi, including assisting in rodent surgeries and experiments.

“What attracted me to the project was the unmet clinical need in (heart attack) recovery,” Aghlara-Fotovat said. “Using hydrogels to deliver therapeutics was an exciting approach that aimed to overcome many challenges in the field of drug delivery. I also saw a clear path to translation into the clinic, which is the ultimate goal of my Ph.D.”

“I think one of the things that attracts students to my lab in particular is the opportunity to do translational work,” Veiseh said. “We work closely with physicians like Dr. Ghanta to address relevant problems to human health.”

Authors

Study co-authors include Maria Jarvis, Sudip Mukherjee and Andrea Hernandez, all of Rice; and Pugazenthi, Christopher Ryan, Vivek Singh and Megumi Mathison, all of Baylor. The research was supported by an American Association of Thoracic Surgery Research Award, the Baylor College of Medicine Cardiovascular Research Institute, the Cancer Prevention Research Institute of Texas (RR160047), the National Institutes of Health (1R01DK120459), a Rice University Academy Fellowship, the Emerson Collective and the National Institutes of Health/National Heart, Lung and Blood Institute Research Training Program in Cardiovascular Surgery (T32 HL139430).

 

The DOI of the Biomaterials Science paper is: 10.1039/D0BM00855A

A copy of the paper is available at: https://doi.org/10.1039/D0BM00855A

 

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Mina Tocalini, 360 Magazine, COVID-19

Rice University’s Charcoal Research

Researchers at Rice University find that charcoal, and other materials described in the American Chemical Society journal ACS Applied Nano Materials, could aid treatment COVID-19 patients.

In the project co-led by Rice chemist James Tour, researchers found oxidized charcoal nanoparticles are not only effective antioxidants, but can also be made from an activated carbon source that is inexpensive, good manufacturing practice (GMP) certified, and already being used in humans to treat acute poisoning.

“That these nanozymes are made from a GMP source opens the door for drug manufacturers,” said Tour, who led the project with A&M neurologist Thomas Kent and UTHealth biochemist Ah-Lim Tsai. “While coal was effective, an issue is that it can have a variety of toxic metallic elements and impurities that are not consistent across samples. And the clusters made from carbon nanotubes are very expensive.”

The researchers noted it may be worthwhile to study the application of their nanozymes to treat the cytokine storms – an excessive immune system response to infection – suspected of contributing to tissue and organ damage in COVID-19 patients.

“While speculative that these particles will be helpful in COVID-19, if administration is timed correctly, they could reduce the damaging radicals that accompany the cytokine storm and could be further chemically modified to reduce other injury-causing features of this disease,” Kent said.

Gang Wu, an assistant professor of hematology at McGovern, and Rice graduate student Emily McHugh are co-lead authors of the study. Co-authors are Vladimir Berka, a senior research scientist at McGovern; Rice graduate students Weiyin Chen, Zhe Wang and Jacob Beckham; Rice undergraduate Trenton Roy; and Paul Derry, an assistant professor at Texas A&M’s Institute of Biosciences and Technology.

Tour is the T.T. and W.F. Chao Chair in Chemistry as well as a professor of computer science and of materials science and nanoengineering at Rice. Kent is the Robert A. Welch Chair Professor in the Institute of Biosciences and Technology at Texas A&M-Houston Campus and an adjunct chemistry professor at Rice and at Houston Methodist Hospital. Tsai is a professor of hematology at UTHealth. Click here to read all of the findings of the Rice University researchers’ work.