First-ever Lab Model of Human Eye Offers Hope For Macular Degeneration Patients (Medicine)

Rochester researchers say their breakthrough could lead to patient-specific treatments.

Age-related macular degeneration (AMD), which leads to a loss of central vision, is the most frequent cause of blindness in adults 50 years of age or older, affecting an estimated 196 million people worldwide. There is no cure, though treatment can slow the onset and preserve some vision.

Recently, however, researchers at the University of Rochester have made an important breakthrough in the quest for an AMD cure. Their first three-dimensional (3D) lab model mimics the part of the human retina affected in macular degeneration.

Their model combines stem cell-derived retinal tissue and vascular networks from human patients with bioengineered synthetic materials in a three-dimensional “matrix.” Notably, using patient-derived 3D retinal tissue allowed the researchers to investigate the underlying mechanisms involved in advanced neovascular macular degeneration, the wet form of macular degeneration, which is the more debilitating and blinding form of the disease.

The researchers have also demonstrated that wet-AMD-related changes in their human retina model could be targeted with drugs.

“Once we have validated this over a large sample, the next hope would be to develop rational drug therapies and potentially even test the efficacy of a specific drug to work for individual patients,” says Ruchira Singh, an associate professor of ophthalmology at the University’s Flaum Eye Institute.

The lab of Danielle Benoit, professor of biomedical engineering and director of the Materials Science Program, engineered the synthetic materials for the matrix and helped configure it, as described in a paper in Cell Stem Cell.

Singh says the findings should help resolve a “huge” debate among researchers in the field who have been trying to determine whether:

  • Defects in the retina itself are responsible for the disease (and if so, which parts of the retina are responsible); or
  • The disease is caused by other “systemic issues,” for example, in blood supply.

Their research points strongly to retinal defects as being responsible—and in particular, to defects in an area called the retinal pigment epithelium (RPE), a pigmented cell layer that nourishes the retina’s photoreceptor cells.

An illustration of the lab model that mimics the part of the human retina affected in macular degeneration. The model combines stem cell-derived retinal tissue and vascular networks from human patients with bioengineered synthetic materials in a 3D “matrix.” (University of Rochester illustration / Michael Osadciw)

Why animal models fail—and a 3D model proved ‘essential’

Two areas of the human eye are affected by AMD. They include the RPE and, beneath the RPE, an underlying support system called the choriocapillaris, composed largely of capillaries that feed the outer retina.

Until now, researchers have relied largely on rodent models. But the anatomy and physiology of the human and rodent retinae are very different. According to Singh, it was essential to create “an in vitro human model of the choriocapillaris layer integrated with the RPE to get the entire complex that is affected by this disease.”

For example, in a previous study, Singh’s lab used only a single retina cell type—patient-derived retinal pigment epithelium (RPE)—to show that symptoms of early and dry forms of AMD could be mimicked in culture, and could be solely caused by dysfunction in the RPE cells. However, the role of the choriocapillarislayer had remained “a mystery that nobody has ever been able to model in culture,” she says.

That’s why it was so important to develop an in vitro and modular human model that could integrate a choriocapillaris layer with the RPE “to get the entire complex that is affected by this disease, so that properties of each individual cell type can be controlled independently,” Singh says.

And that’s why Benoit’s lab, which specializes in creating synthetic hydrogels for cell culture, tissue engineering, and target drug delivery, was important.

Benoit’s lab engineered the 3D matrix in which the choriocapillaris could be safely placed and also “properly oriented in the overall vasculature,” Benoit says. “We also facilitated the adhesion of the RPE cells within the model. It was a small, but important contribution. A three-dimensional model was essential to describe the really amazing things that have been identified and discovered using this model.”

The findings offer a possible resolution to the debate over the causes of macular degeneration. The researchers now show for the first time that defects in RPE cells alone are sufficient to cause the disease. “You can have completely normal choriocapillaris, but if your RPE’s are dysfunctional it will cause the choriocapillaristo dysfunction,” Singh says.

Similarly, using blood samples from patients with wet AMD in the human retina model, their data for the first time also shows that blood-derived factors from patients can independently contribute to the development and progression of wet AMD.

The collaborations, Singh says, have succeeded in

  • Creating an accurate human model of the RPE/choriocapillaris complex
  • Confirming that RPE and mesenchymal stem cells play a role in the development of the choriocapillarislayer
  • Mimicking aspects of macular degeneration in the human model
  • Understanding the role of specific cells types and blood-derived factors in the development of macular degeneration
  • Targeting the disease, using a drug in a patient derived cell model

World leadership in vision science

The latest research by Singh and Benoit builds on the University of Rochester’s long tradition as a world leader in vision science.

In the 1990s, for example, David Williams, the William G. Allyn Professor of Medical Optics, and his group applied adaptive optics—first used in telescopes to more clearly see through the Earth’s atmosphere—to image individual retinal cells, right down to single photoreceptors in the living human retina. The work of Williams and his team has had a far-reaching effect on procedures to improve vision and is applied throughout the world in Lasik procedures today.

That legacy attracted both Singh and Benoit to Rochester, but so, too, did another factor: the proximity of the engineering and science departments and the Medical Center—located across an avenue from one another—and the chance to work together. Benoit says that proximity was a “critical” factor in her decision to join the Department of Biomedical Engineering in 2010. Singh says the opportunity to collaborate with Benoit was one of the main reasons she decided to join the Medical Center seven years ago.

It’s useful in forging other collaborations as well. Vision science at the University now involves a synergy of science, engineering and medicine across various departments including brain and cognitive sciences, neurobiology and anatomy, and ophthalmology, engaging about 100 Rochester faculty members. The Center for Visual Science, and its ARIA lab, directed by Williams, collaborates closely with the Medical Center’s Flaum Eye Institute and is the hub of these collaborations.

Funding support for their paper comes from both private foundations and the National Institutes of Health. The private foundations are BrightFocus Foundation, Foundation of Fighting Blindness, Knights Templar eye foundation, and the Retina Research Foundation and Research to Prevent Blindness.

Other collaborators on the paper include:

  • At the University of Rochester: Lead author Kannan V. Manian, Chad Galloway, Sonal Dalvi, Anthony A. Emanuel, Jared A. Mereness, Whitney Spencer, Lauren Winschel, Celia Soto, Yiming Li, Yuanhui Song, William DeMaria, and Mina Chung.
  • At the University of Wisconsin: Akhilesh Kumar, Igor Slukvin, Michael P. Schwartz, and William L. Murphy.
  • At the Cleveland Clinic Cole Eye Institute: Bela-Anand Apte

Featured image: University of Rochester researchers have created the first 3D lab model that mimics the part of the human retina affected in macular degeneration, the most frequent cause of blindness in adults 50 years of age or older. (Getty Images photo)


Reference: Kannan V. Manian, Chad A. Galloway et al., “3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration”, Cell, 2021. DOI: https://doi.org/10.1016/j.stem.2021.02.006


Provided by University of Rochester

Common Medications Contain Animal Byproducts, Study Finds (Medicine)

More physicians and pharmacists are advocating for patients to be made aware of animal byproducts contained in common medications, according to new research in the Journal of Osteopathic Medicine. Common medications, including widely used blood thinners and hormones, are often derived from animal byproducts and prescribed without consulting the patient about their beliefs.

“Patients deserve to know what their medications are made of, yet this information is rarely shared,” said Sara Reed, student doctor at Lincoln Memorial University (LMU) DeBusk College of Osteopathic Medicine and an author of the paper. “Putting the patient first means communicating with them about the medicine recommended for their care, and in some cases, prescribing an alternative option.”

Common Animal-derived Medications

Heparinoids are a class of medication primarily derived from pigs. These drugs are routinely used as a blood thinner to prevent blood clots and are given in many settings, including following surgery, a heart attack, or to prevent the further development of clots.

Also common are conjugated estrogens, which may be used to treat moderate to severe hot flashes and other symptoms of menopause. They are equine-derived hormones.

“Generally, patients who are prescribed various hormone treatments may want to consult their physician regarding the contents,” said Mary Beth Babos, PharmD, professor of pharmacology at LMU, and lead author of the paper. “For example, there are no completely animal-free oral thyroid hormones on the market.”

Existing Guidelines

While the U.S. does not have formal recommendations, other nations have published guidelines to address pharmaceuticals of animal origin. The United Kingdom’s first guidelines were published in 2004 and Australia’s guidelines were published in 2007 and updated again in 2019. However, guidelines from the FDA remain unavailable.

Cultural Competency

Because some patients adhere to religious doctrine that recommends avoiding certain animal byproducts, the study authors reviewed prior medical research to identify the stated positions of leadership of the major world religions. According to their findings, many religions discourage the use of products derived from animals when not required to save human life.

  • Jewish and Muslim leaders agree that the use of products derived from pigs—normally prohibited by both religions—are acceptable only when needed to protect human life.
  • The Hindu Council of Australia does not consider bovine products, including medications derived from cows, acceptable.
  • Sikh leaders and leaders of the Hindu Vaishnav sect object to the use of medication or surgical dressing derived from animal sources, which is waived in emergency situations or in routine treatment where no alternative exists.
  • Many Buddhists of the Theravada sect and Christians of the Seventh Day Adventist sect who practice vegetarianism as part of their faith may individually reject animal-derived medical products.
  • Leaders of the Jehovah’s Witness sect emphasized that adherents to this faith would reject blood-derived products.

“In the absence of governmental guidance, we hope this research will help physicians and prescribers start the conversation with patients about whether they accept animal-derived products,” said Reed. “Ultimately, it is the patient who should determine if a medication is appropriate for their lifestyle.”


Reference: Mary Beth Babos , Joseph D. Perry , Sara A. Reed , Sandra Bugariu , Skyler Hill-Norby , Mary Jewell Allen , Tara K. Corwell , Jade E. Funck , Kaiser F. Kabir , Katherine A. Sullivan , Amber L. Watson and K. Kelli Wethington, “Animal-derived medications: cultural considerations and available alternatives”, De Gruyter | Published online: March 8, 2021DOI: https://doi.org/10.1515/jom-2020-0052


Provided by American Osteopathic Association


About the Journal of Osteopathic Medicine

The Journal of Osteopathic Medicine, founded in 1901 and known for 119 years as The Journal of the American Osteopathic Association, is the premier scholarly, peer-reviewed publication of the osteopathic medical profession. JOM conducts peer review of academic research manuscripts from a wide variety of medical specialties, covering the full spectrum of clinical settings in which osteopathic physicians practice. All submissions are vetted by a distinguished group of Section Editors led by Editor-in-Chief Ross Zafonte, DO, and supported by a full Editorial Board.

Diabetes Drug May Be A New Weapon Against HIV (Medicine)

Research from the UNC School of Medicine lab of Jenny Ting, PhD, shows that widely used drug metformin reduces metabolism of infected T cells to suppress HIV replication.

A team led by scientists at the UNC School of Medicine discovered an important vulnerability of the AIDS-causing retrovirus HIV, and has shown in preclinical experiments that a widely used diabetes drug, metformin, seems able to exploit this vulnerability.

The scientists, whose study is published in Nature Immunology, found that HIV, when it infects immune cells called CD4 T cells, helps fuel its own replication by boosting a key process in the cells’ production of chemical energy. They also found that the diabetes drug metformin inhibits the same process and thereby suppresses HIV replication in these cells, in both cell-culture and mouse experiments.

“These findings suggest that metformin and other drugs that reduce T cell metabolism might be useful as adjunct therapies for treating HIV,” said study co-first author Haitao Guo, PhD, assistant professor in the UNC Department of Genetics at the UNC School of Medicine.

The co-first author of the study was Qi Wang, PhD, postdoctoral research associate. The study’s co-senior authors were Jenny Ting, PhD, William R. Kenan, Jr. Distinguished Professor in the Department of Genetics at UNC-Chapel Hill, and Lishan Su, PhD, professor of pharmacology at the University of Maryland School of Medicine and formerly of the UNC School of Medicine.

About 38 million people around the world are living with HIV infection, according to the World Health Organization’s most recent estimates. Doctors currently treat these infections with combinations of antiretroviral drugs to suppress HIV replication.

However, many patients despite this treatment show signs of residual viral replication and immune impairment. Even patients who respond well to antiretroviral drugs must take them indefinitely, since HIV inscribes itself into the DNA of some infected cells, and the drugs cannot clear this viral genetic “reservoir.” Moreover, the toxicity of anti-HIV drugs means that many patients can take them only intermittently. Thus, despite progress, there is still much room for improvement in HIV treatment.

A possible new approach to treating HIV is not to attack it directly but to make the cells it infects less hospitable to viral replication. For example, other research showed that HIV boosts CD4 cell energy production, apparently to enhance the virus’s ability to replicate within those cells. Guo and colleagues in their study sought to understand better how HIV does this, and whether reversing this metabolic effect could suppress HIV.

In collaboration with Rafick-Pierre Sekaly, PhD, and Khader Ghneim at Case Western University, they analyzed CD4-cell gene expression data from a study of HIV-infected people in Africa and Asia and found that the gene-expression patterns most closely related to poor outcomes among these patients involved an energy-production process called oxidative phosphorylation.

They then found that drugs and other chemical compounds that inhibit oxidative phosphorylation in CD4 cells can inhibit HIV’s ability to replicate in these cells. One of these drugs is the diabetes drug metformin, which is one of the world’s most widely prescribed drugs, is considered safe and well tolerated, and is also inexpensive. Guo and colleagues confirmed with further experiments in primary human CD4 cells, and in mice with human CD4 cells, that metformin suppresses HIV replication in these cells.

The researchers also examined a prior study of HIV patients taking antiretroviral therapy to discover that, after six months of treatment, the patients that had type 2 diabetes – many of whom would have been taking metformin – had on average 33 percent lower levels of HIV in the blood, compared with non-diabetic patients in the cohort. The diabetic patients also, on average, had higher baseline CD4 cell levels and quicker recoveries of these levels with antiretroviral treatment.

“Those real-world findings are consistent with the idea that metformin has a significant anti-HIV effect,” Ting said.

The scientists ultimately traced HIV’s ability to increase oxidative phosphorylation in CD4 cells to its boosting of the levels of NLRX1, a protein associated with mitochondria – tiny oxygen reactors that help cells produce the chemical energy they need. NLRX1 appears to be a key metabolic switch that HIV uses to enhance its replication in CD4 cells, which in turn makes it a potential target for future HIV treatments.

“This work shows the importance of CD4 cell metabolism in HIV, and suggests that it may be targetable, for example with repurposed drugs such as metformin, to reduce HIV viral load and restore these disease-fighting CD4 cells,” Ting said.

The researchers plan to continue preclinical studies of metformin’s potential as an anti-HIV treatment, conceivably a therapy that could reduce the need for toxic antiretrovirals and could be given to patients earlier to reduce HIV reservoir formation. They note that Canadian researchers, using a very different rationale – that metformin can help preserve CD4 cells by altering the composition of gut bacteria to reduce inflammation and chronic T cell activation – have conducted a clinical trial of metformin in non-diabetic HIV patients, but have not yet published results on its efficacy in improving markers of HIV infection.

Other authors of the Nature Immunology paper are Li Wang, Elena Rampanelli, Elizabeth Holley-Guthrie, Liang Cheng, Carolina Garrido, David Margolis, Leigh Eller, Merlin Robb, Rafick-Pierre Sekaly, and Xian Chen. Ting is a member of the UNC Lineberger Comprehensive Cancer Center.

Funding was provided by the National Institutes of Health (R01-AI029564, U19AI109965, AI127346, DK119937, P30 AI50410).


Reference: Guo, H., Wang, Q., Ghneim, K. et al. Multi-omics analyses reveal that HIV-1 alters CD4+ T cell immunometabolism to fuel virus replication. Nat Immunol (2021). https://doi.org/10.1038/s41590-021-00898-1


Provided by UNC School of Medicine

Black Hole Key to Galaxies Behemoths (Cosmology / Astronomy)

A new black hole breaks the record –– not for being the smallest or the biggest –– but for being right in the middle.

The recently discovered ‘Goldilocks’ black hole is part of a missing link between two populations of black holes: small black holes made from stars and supermassive giants in the nucleus of most galaxies.

In a joint effort, researchers from the University of Melbourne and Monash University have uncovered a black hole approximately 55,000 times the mass of the sun, a fabled “intermediate-mass” black hole.

The discovery was published today in the paper Evidence for an intermediate mass black hole from a gravitationally lensed gamma-ray burst”in the journal, Nature Astronomy.

Lead author and University of Melbourne PhD student, James Paynter, said the latest discovery sheds new light on how supermassive black holes form. “While we know that these supermassive black holes lurk in the cores of most, if not all galaxies, we don’t understand how these behemoths are able to grow so large within the age of the Universe,” he said.

The new black hole was found through the detection of a gravitationally lensed gamma-ray burst.

The gamma-ray burst, a half-second flash of high-energy light emitted by a pair of merging stars, was observed to have a tell-tale ‘echo’. This echo is caused by the intervening intermediate-mass black hole, which bends the path of the light on its way to Earth, so that astronomers see the same flash twice.

Powerful software developed to detect black holes from gravitational waves was adapted to establish that the two flashes are images of the same object.

“This newly discovered black hole could be an ancient relic –– a primordial black hole –– created in the early Universe before the first stars and galaxies formed,” said study co-author, Professor Eric Thrane from the Monash University School of Physics and Astronomy and Chief Investigator for the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav).

“These early black holes may be the seeds of the supermassive black holes that live in the hearts of galaxies today.”

Paper co-author, gravitational lensing pioneer, Professor Rachel Webster from the University of Melbourne said the findings have the potential to help scientists make even greater strides.

“Using this new black hole candidate, we can estimate the total number of these objects in the Universe. We predicted that this might be possible 30 years ago, and it is exciting to have discovered a strong example.”

The researchers estimate that some 46,000 intermediate mass black holes are in the vicinity of our Milky Way galaxy.

Featured image: The new black hole was found through the detection of a gravitationally lensed gamma-ray burst. Image: Carl Knox, OzGrav.


Reference: Paynter, J., Webster, R. & Thrane, E. Evidence for an intermediate-mass black hole from a gravitationally lensed gamma-ray burst. Nat Astron (2021). https://doi.org/10.1038/s41550-021-01307-1


Provided by University of Melbourne

Dark Matter Is The Most Likely Source of Excess of Gamma Rays From Galactic Center (Cosmology / Astronomy)

In the recent past, space missions dedicated to the study of astrophysical signals in the high-energy spectrum revealed a series of enigmatic excesses not predicted by the theoretical models. In order to find an explanation for these anomalies, many solutions have been proposed. The most exciting hypothesis invokes the contribution of the elusive dark matter, the mysterious form of matter 4 times more abundant than ordinary one and of which we have so far detected only its gravitational effects. Two recent theoretical studies carried out by Mattia di Mauro, researcher of the Turin division of INFN, one of which appeared today in Physical Review D, confirm that this explanation is compatible with measured excesses, further demonstrating that it is not disproven by potential discrepancies between theoretical and observational data. The results obtained are based on an innovative and refined analysis comparing data acquired in the last 11 years by the main instrument aboard NASA’s Fermi, the Fermi Large Area Telescope (LAT), with measurements of other astronomical anomalies recorded by the orbiting Pamela detector and by the Alpha Magnetic Spectrometer experiment (AMS-02) aboard the International Space Station. Pamela and AMS are managed by international collaborations in which INFN plays a decisive role.

Starting from 2009, the year in which Fermi measurements showed a surplus of photons with energies equal to or greater than 1 GeV (2000 times the mass of an electron) coming from the center of our galaxy, the astrophysics community has tried to explain the observations in several ways, including the possible presence of thousands of weak pulsars near the galactic center and the potential gamma-ray contribution provided by dark matter. These analyses were subject to great uncertainty since they referred to models of the so-called astrophysical gamma-ray background, produced by cosmic rays or by known sources, which, although capable of including a certain variability, are subject to great error.

In order to describe the gamma-ray excess properties more precisely and to evaluate whether it is really compatible with dark matter, the new study relied on the broadest set of data collected in the last year by the LAT, and used an analysis technique that minimizes the uncertainties of the astrophysical background by adopting multiple models. “The analysis methodology used,” explains Mattia di Mauro, “has provided very relevant information about the spatial distribution of excess gamma radiation, which can explain what generates the excess of high-energy photons in the Galactic center. If the excess was, for example, caused by the interaction between cosmic rays and atoms, we would expect to observe its greater spatial distribution at lower energies and its lower diffusion at higher energies due to the propagations of cosmic particles. My study, on the other hand, underlines how spatial distribution of the excess does not change as a function of energy. This aspect had never been observed before and could be explained by dark matter presence dark matter interpretation. This is because we think the particles composing the dark matter halo should have similar energies. The analysis clearly shows that the excess of gamma rays is concentrated in the Galactic center, exactly what we would expect to find in the heart of the Milky Way if dark matter is in fact a new kind of particle.

A second study, which will be published in the same journal, examines the validity of the dark matter hypothesis using the predictions from a larger model that describes possible particle interactions of this elusive component of the universe. A theoretical model demonstrated how the existence of dark matter particles is not disproven by other anomalies recorded in the astrophysical background. These include the excess of positrons measured by Pamela and AMS-02, if attributed to a surplus of dark matter, and the non-detection of high-energy photons from dwarf galaxies close to ours, whose stellar motions imply the presence of high concentrations of dark matter. “Starting from the physical model developed in this second study,” Di Mauro continues, “after considering different results for the interaction and annihilation of dark matter particles, alternatives that would precede the production of high-energy photons, we verified which of these possibilities best accorded with the galactic center’s excess gamma rays, while also considering the surplus of positrons and the non-detection of gamma rays from dwarf galaxies. This comparison has made able to derive accurate properties of the dark matter, properties compatible with the galactic center excess and the upper limits found with other particles data.”

Link: (1) Mattia Di Mauro. Characteristics of the Galactic Center excess measured with 11 years of Fermi -LAT data, Physical Review D (2021). https://journals.aps.org/prd/abstract/10.1103/PhysRevD.103.063029 (2) Multimessenger constraints on the dark matter interpretation of the Fermi-LAT Galactic center excess: arxiv.org/abs/2101.11027 arXiv:2101.11027v1 [astro-ph.HE] https://arxiv.org/abs/2101.11027

Featured image credit: ESO/FERMI-LAT


Provided by Infn

MIT Astronomers Discover New Galaxy Clusters Hiding in Plain Sight (Astronomy)

Lesson learned from the CHiPS survey must inform future cluster searches, researchers say.

MIT astronomers have discovered new and unusual galactic neighborhoods that previous studies overlooked. Their results, published today, suggest that roughly 1 percent of galaxy clusters look atypical and can be easily misidentified as a single bright galaxy. As researchers launch new cluster-hunting telescopes, they must heed these findings or risk having an incomplete picture of the universe.

Galaxy clusters contain hundreds to thousands of galaxies bound together by gravity. They move through a hot soup of gas called the intracluster medium, which contains more mass than all the stars in all the galaxies within it. This hot gas fuels star formation as it cools and emits X-ray radiation that we can observe with space-based telescopes. 

This bright gas cloud creates a fuzzy halo of X-rays around galaxy clusters, making them stand out from more discrete point sources of X-rays produced by, for example, a star or quasar. However, some galactic neighborhoods break this mold, as MIT Associate Professor Michael McDonald learned nine years ago.

In 2012, McDonald discovered a cluster unlike any other, which shone bright like a point source in the X-ray. Its central galaxy hosts a ravenous black hole that consumes matter and spews X-rays so bright as to drown out the diffuse radiation of the intracluster medium. In its core, the cluster forms stars at a rate roughly 500 times higher than most other clusters, giving it the blue glow of a young star population instead of the typical red hue of aging stars.

“We’d been looking for a system like this for decades,” McDonald says of the Phoenix cluster. And yet, it had been observed and passed over years prior, assumed to be a single galaxy instead of a cluster. “It’d been in the archive for decades and no one saw it. They were looking past it because it didn’t look right.”

And so, McDonald wondered, what other unusual clusters might be lurking in the archive, waiting to be found? Thus, the Clusters Hiding in Plain Sight (CHiPS) survey was born.

Taweewat Somboonpanyakul, a graduate student in McDonald’s lab, devoted his entire PhD to the CHiPS survey. He began by selecting potential cluster candidates from decades of X-ray observations. He used existing data from ground-based telescopes in Hawaii and New Mexico, and visited the Magellan telescopes in Chile to take new images of the remaining sources, hunting for neighboring galaxies that would reveal a cluster. In the most promising cases, he zoomed in with higher-resolution telescopes such as the space-based Chandra X-Ray Observatory and Hubble Space Telescope.

After six years, the CHiPS survey has now come to a close. Today in The Astrophysical Journal, Somboonpanyakul published the survey’s cumulative results, which include the discovery of three new galaxy clusters. One of these clusters, CHIPS1911+4455, is similar to the rapidly-star-forming Phoenix cluster and was described in a paper in January in The Astrophysical Journal Letters. It’s an exciting finding since astronomers know of just a few other Phoenix-like clusters. This cluster invites further study, however, as it has a twisted shape with two extended arms, whereas all other rapidly-cooling clusters are circular. The researchers believe it may have collided with a smaller galaxy cluster. “It’s super unique compared to all the galaxy clusters that we now know,” says Somboonpanyakul.

In all, the CHiPS survey revealed that older X-ray surveys missed roughly 1 percent of galactic neighborhoods because they look different than the typical cluster. This can have significant implications, since astronomers study galaxy clusters to learn about how the universe expands and evolves. “We need to find all the clusters to get those things right,” McDonald explains. “Ninety-nine percent completion isn’t enough if you want to push the frontier.”

As scientists discover and study more of these unusual galaxy clusters, they may better understand how they fit into the broader cosmic picture. At this point, they don’t know whether a small number of clusters are always in this strange, Phoenix-like state, or if this is perhaps a typical phase that all clusters undergo for a short period of time — roughly 20 million years, a fleeting moment by spacetime standards. It’s difficult for astronomers to tell the difference, as they only get a single snapshot of each cluster nearly frozen in time. But with more data, they can make better models of the physics governing these galactic neighborhoods.

The conclusion of the CHiPS survey coincides with the launch of a new X-ray telescope, eROSITA, which aims to grow our catalogue of clusters from a few hundred to tens of thousands. But unless they change the way they look for those clusters, they will miss hundreds that deviate from the norm. “The people that are building out the cluster searches for this new X-ray telescope need to be aware of this work,” says McDonald. “If you miss 1 percent of the clusters, there’s a fundamental limit to how well you can understand the universe.”

This research was supported, in part, by the Kavli Research Investment Fund at MIT, and by NASA through the Guest Observer programs for the Chandra X-ray Observatory and Hubble Space Telescope.

Featured image: The newly discovered galaxy cluster CHIPS1911+4455 has a unique twisted shape compared to other rapidly cooling galaxy clusters. This image was taken with the Hubble Space Telescope. Credit: NASA/ESA/Hubble Heritage Team


Reference: Taweewat Somboonpanyakul, Michael Mcdonald et al., “The Clusters Hiding in Plain Sight (CHiPS) Survey: Complete Sample of Extreme BCG Clusters”, The Astrophysical Journal, Volume 910, Number 1, 2021. https://iopscience.iop.org/article/10.3847/1538-4357/abe1bc


Provided by MIT

Tires Turned Into Graphene That Makes Stronger Concrete (Material Science)

Rice University lab’s optimized flash process could reduce carbon emissions

This could be where the rubber truly hits the road.

Rice University scientists have optimized a process to convert waste from rubber tires into graphene that can, in turn, be used to strengthen concrete.

The environmental benefits of adding graphene to concrete are clear, chemist James Tour said.

“Concrete is the most-produced material in the world, and simply making it produces as much as 9% of the world’s carbon dioxide emissions,” Tour said. “If we can use less concrete in our roads, buildings and bridges, we can eliminate some of the emissions at the very start.”

Recycled tire waste is already used as a component of Portland cement, but graphene has been proven to strengthen cementitious materials, concrete among them, at the molecular level.

While the majority of the 800 million tires discarded annually are burned for fuel or ground up for other applications, 16% of them wind up in landfills.

“Reclaiming even a fraction of those as graphene will keep millions of tires from reaching landfills,” Tour said.

The “flash” process introduced by Tour and his colleagues in 2020 has been used to convert food waste, plastic and other carbon sources by exposing them to a jolt of electricity that removes everything but carbon atoms from the sample.

Those atoms reassemble into valuable turbostratic graphene, which has misaligned layers that are more soluble than graphene produced via exfoliation from graphite. That makes it easier to use in composite materials.

Rubber proved more challenging than food or plastic to turn into graphene, but the lab optimized the process by using commercial pyrolyzed waste rubber from tires. After useful oils are extracted from waste tires, this carbon residue has until now had near-zero value, Tour said.

Rice scientists optimized a process to turn rubber from discarded tires into turbostratic flash graphene.  Courtesy of the Tour Research Group

Tire-derived carbon black or a blend of shredded rubber tires and commercial carbon black can be flashed into graphene. Because turbostratic graphene is soluble, it can easily be added to cement to make more environmentally friendly concrete.

The research led by Tour and Rouzbeh Shahsavari of C-Crete Technologies is detailed in the journal Carbon.

The Rice lab flashed tire-derived carbon black and found about 70% of the material converted to graphene. When flashing shredded rubber tires mixed with plain carbon black to add conductivity, about 47% converted to graphene. Elements besides carbon were vented out for other uses.

The electrical pulses lasted between 300 milliseconds and 1 second. The lab calculated electricity used in the conversion process would cost about $100 per ton of starting carbon.

The researchers blended minute amounts of tire-derived graphene — 0.1 weight/percent (wt%) for tire carbon black and 0.05 wt% for carbon black and shredded tires — with Portland cement and used it to produce concrete cylinders. Tested after curing for seven days, the cylinders showed gains of 30% or more in compressive strength. After 28 days, 0.1 wt% of graphene sufficed to give both products a strength gain of at least 30%.

“This increase in strength is in part due to a seeding effect of 2D graphene for better growth of cement hydrate products, and in part due to a reinforcing effect at later stages,” Shahsavari said.

Rice graduate student Paul Advincula is lead author of the paper. Co-authors are Rice postdoctoral researcher Duy Luong and graduate student Weiyin Chen, and Shivaranjan Raghuraman of C-Crete. 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.

The Air Force Office of Scientific Research and the Department of Energy’s National Energy Technology Laboratory supported the research.

Read the abstract at https://www.sciencedirect.com/science/article/abs/pii/S0008622321003249.

Featured image: A transmission electron microscope image shows the interlayer spacing of turbostratic graphene produced at Rice University by flashing carbon black from discarded rubber tires with a jolt of electricity. Courtesy of the Tour Research Group


Provided by Rice University

How Cells Transport Molecules With ‘Active Carpets’? (Chemistry)

New research provides insights into the process of diffusion in living systems, with implications from novel active coatings to understanding how pathogens are cleared from lungs.

A drop of food coloring slowly spreading in a glass of water is driven by a process known as diffusion. While the mathematics of diffusion have been known for many years, how this process works in living organisms is not as well understood.

Now, a study published in Nature Communications provides new insights on the process of diffusion in complex systems. The result of a collaboration between physicists at Penn, the University of Chile, and Heinrich Heine University Düsseldorf, this new theoretical framework has broad implications for active surfaces, such as ones found in biofilms, active coatings, and even mechanisms for pathogen clearance.

Diffusion is described by Fick’s laws: Particles, atoms, or molecules will always move from a region of high to low concentration. Diffusion is one of the most important ways that molecules move within the body. However, for the transport of big objects over large distances, standard diffusion becomes too slow to keep up.

“That’s when you need active components to help transport things around,” says study co-author Arnold Mathijssen. In biology, these actuators include cytoskeletal motors that move cargo vesicles in cells, or cilia that pump liquid out of human lungs. When many actuators accumulate on a surface, they are known as “active carpets.” Together, they can inject energy into a system in order to help make diffusion more efficient.

Mathijssen, whose research group studies the physics of pathogens, first became interested in this topic while studying biofilms with Francisca Guzmán-Lastra, an expert on the physics of active matter, and theoretical physicist Hartmut Löwen. Biofilms are another example of active carpets since they use their flagella to create “flows” that pump liquid and nutrients from their environment. Specifically, the researchers were interested in understanding how biofilms are able to sustain themselves when access to nutrients is limited. “They can increase their food uptake by creating flows, but this also costs energy. So, the question was: How much energy do you put in to get energy out?” says Mathijssen.

But studying active carpets is difficult because they don’t align neatly with Fick’s laws, so the researchers needed to develop a way to understand diffusion in these non-equilibrium systems, or ones that have added energy. “We thought that we could generalize these laws for enhanced diffusion, when you have systems that do not follow Fick’s laws but may still follow a simple formula that is widely applicable to many of these active systems,” Mathijssen says.

After figuring out how to connect the math needed to understand both bacterial dynamics and Fick’s laws, the researchers developed a model similar to the Stokes-Einstein equation, which describes the relationship with temperature and diffusion, and found that microscopic fluctuations could explain the changes they saw in particle diffusion. Using their new model, the researchers also found that the diffusion generated by these small movements is incredibly efficient, allowing bacteria to use just a small amount of energy to gain a large amount of food.

“We’ve now derived a theory that predicts the transport of molecules inside cells or close to active surfaces. My dream would be that these theories would be applied in different biophysical settings,” says Mathijssen. His new research lab at Penn will start working on follow-up experiments to test out these new models. They plan to study active diffusion both in biological and engineered microscopic systems.

Mathijssen, who is also involved on a project related to the spread of COVID-19 in food-processing facilities, says that the cilia in lungs are another important example of active carpets in biology, especially since they serve as the first line of defense against pathogens like COVID-19. He says, “That would be another very important thing to test, whether this theory of active carpets may be linked to the theory of pathogen clearance in the airways.”

This research was supported by the United States Department of Agriculture (USDA-NIFA AFRI grants 2020-67017-30776 and 2020-67015-32330) and Human Frontier Science Program Fellowship LT001670/2017 and an International Research Travel Award from the American Physical Society.

Featured image: An active carpet made of molecular motors (top) generates strong flows, which enhances the diffusion of nearby particles as modeled by the resulting flow fields (bottom). © Arnold Mathijssen


Reference: Guzmán-Lastra, F., Löwen, H. & Mathijssen, A.J.T.M. Active carpets drive non-equilibrium diffusion and enhanced molecular fluxes. Nat Commun 12, 1906 (2021). https://www.nature.com/articles/s41467-021-22029-y https://doi.org/10.1038/s41467-021-22029-y


Provided by University of Pennsylvania

First Detailed Look At Crucial Enzyme Advances Cancer Research (Biology)

In order to develop more effective drugs against a range of cancers, researchers have been investigating the molecular structure of many diseased-linked enzymes in the body. An intriguing case in point is Taspase 1, a type of enzyme known as a protease. The primary duty of proteases is to break down proteins into smaller peptide snippets or single amino acids.

Taspase 1 appears to play a vital role in a range of physiological processes, including cell metabolism, proliferation, migration and termination. The normal functioning of Taspase 1 can go awry however, leading to a range of diseases, including leukemia, colon and breast cancers, as well as glioblastoma, a particularly lethal and incurable malignancy in the brain.

Because Taspase 1 dysregulation is increasingly implicated in the genesis and metastasis of various cancers, it has become an attractive candidate for drug development. But before this can happen, researchers will need a highly detailed blueprint of the structure of this protease.

In a new study appearing in the Cell Press journal Structure, researchers from Arizona State University describe their investigations, which reveal the structure of Taspase 1 as never before.

The study unveils, for the first time, the catalytically active 3D structure of Taspase 1, revealing a previously unexplored region that is essential for the functioning of the molecule. The structure was solved using X-ray crystallography and confirmed with electron microscopy.

Jose Martin-Garcia is currently a researcher with the Department of Crystallography and Structural Biology at the Spanish National Research Council, Madrid. © ASU

Petra Fromme, director of the Biodesign Center for Applied Structural Discovery,  highlights the great importance of the work: “I am so excited that we were able to solve the first structure of the functional active enzyme, as it will have huge implications for the structure-based development on novel anti-cancer drugs.”

The study results show that reducing this critical helical region of Taspase 1 limits protease activity, while eliminating the helical region deactivates Taspase 1 functioning altogether. Earlier research suggests that disabling Taspase 1 activity to block the progression of cancer could be achieved without harmful side-effects.

“We have reported the importance of a previously unobserved long fragment of the protein in  the catalytic activity of Taspase1, which can be used as attractive target to inhibit Taspase1,” according Jose Martin-Garcia,  lead scientist on the project and co-correponding author with professor Fromme. “The crystal structure of the active Taspase1 reported in our article will be greatly beneficial to advance the design of Taspase1 inhibitors for anti-cancer therapy.”

Martin-Garcia is currently a researcher with the Department of Crystallography and Structural Biology at the Spanish National Research Council, Madrid.

Fromme and Martin-Garcia are joined by their Biodesign collaborators Nirupa Nagaratnam, Rebecca Jernigan, Brent L. Nannenga and Darren Thifault, along with their multi-institute colleagues.

Featured image: Petra Fromme is the director of the Biodesign Center for Applied Structural Discovery. She is also a Regents Professor at ASU’s School of Molecular Sciences. © ASU


Provided by Arizona State University