Breaking Research

Faculty of Arts & Science

Earth Sciences

Global

Recent satellite data reveal that the Konya Basin in the Central Anatolian Plateau of Türkiye is continually being reshaped over millions of years, according to a new analysis led by Earth scientists at the ��߲ݴ�ý.

The researchers say experimental simulations – combined with geological, geophysical and geodetic data – explain the enigmatic sinking of the basin within the rising plateau interior and further suggests a new class of plate tectonics that has implications for other planets that do not have Earth-like plates such as Mars and Venus.

The study, published in Nature Communications, shows the sinking in the region is due to multi-stage lithospheric dripping – a phenomenon named for the instability of rocky material that makes up Earth’s crust and upper mantle. As dense rock fragments beneath the surface detach and sink into the more fluid layer of the planet’s mantle, major landforms such as basins and mountainous folding of the crust form at the surface.

“Looking at the satellite data, we observed a circular feature at the Konya Basin where the crust is subsiding or the basin is deepening,” says lead author Julia Andersen, a PhD candidate in U of T’s department of Earth sciences in the Faculty of Arts & Science.

“This prompted us to look at other geophysical data beneath the surface where we saw a seismic anomaly in the upper mantle and a thickened crust, telling us there is high-density material there and indicating a likely mantle lithospheric drip.”

Artist’s impression of the multi-stage lithospheric dripping process in Central Anatolia (illustration by Nevena Niagolova)

The results echo a similar investigation by the researchers into the formation of the Arizaro Basin in the Andes Mountains of South America, suggesting the phenomenon can occur anywhere on the planet and explains tectonic processes typically found within mountain plateau regions.

Past studies show the Central Anatolian Plateau has risen by as much as one kilometre over the past 10 million years because of the lithospheric dripping phenomenon.

“As the lithosphere thickened and dripped below the region, it formed a basin at the surface that later sprang up when the weight below broke off and sank into the deeper depths of the mantle,” says Russell Pysklywec, a professor in the department of Earth sciences and a co-author of the study.

“We now see the process is not a one-time tectonic event and that the initial drip seems to have spawned subsequent daughter events elsewhere in the region, resulting in the curious rapid subsidence of the Konya Basin within the continuously rising plateau of Türkiye.”

Andersen adds that the new findings suggest a connection between plateau uplift and basin formation events through the evolution of primary and secondary lithospheric removal. “Essentially, subsidence is occurring alongside the ongoing uplifting of the plateau.”

Andersen and study co-authors, including colleagues at Istanbul Technical University and Çanakkale Onsekiz Mart University in Türkiye, arrived at their findings after recreating the dripping process in laboratory experiments and analyzing their observations.

They built laboratory analogue models to establish how the process may have unfolded based on the data provided by the new measurements, filling a plexiglass tank with polydimethylsiloxane (PDMS) – a silicone polymer fluid approximately 1,000 times thicker than table syrup – to serve as Earth’s fluid lower mantle, adding a mixture of PDMS and modelling clay to replicate the upper-most solid section of the mantle, finishing with a sand-like layer on top made from ceramic and silica spheres to serve as Earth’s crust.

Artist’s impression of two types of lithospheric drip: one produces thickening and uplift of Earth’s crust, while the other results in the formation of a basin at the surface without horizontal deformation (illustration by Julia Andersen/��߲ݴ�ý)

The researchers activated the model by inserting a high-density seed into the PDMS and modelling clay layer to initiate a drip that was subsequently pulled downward by gravity. A set of cameras were positioned above and beside the tank to record any changes over time, capturing a high-resolution image roughly every minute.

“Within 10 hours, we observed an initial phase of dripping, which we call a primary drip. After that primary drip touched the bottom of the box, we saw a second drip had begun to sink to the bottom after 50 hours,” says Andersen. “Both the primary and secondary drip were not causing any horizontal deformation in our artificial crust, which we expect is typically associated with a mantle lithospheric drip.”

The researchers already knew that the primary drip had caused changes in surface topography of the experiment, and wanted to know if the secondary drip would have any effect on the surface since it was a smaller sized drip than the primary drip. “What we noticed was that over time, this secondary drip did pull the crust downward and started to create a basin, despite no horizontal movements in the crust at the surface,” Andersen says. “The findings show these major tectonic events are linked, with one lithospheric drip potentially triggering a host of further activity deep in the planetary interior.”

'Narrative reversal' is key to telling a great story in books, films and TV shows: Study

Christopher.Sorensen — Tue, 17 Sep 2024 14:59:38 +0000

'Narrative reversal' is key to telling a great story in books, films and TV shows: Study

Christopher.Sorensen Tue, 09/17/2024 - 10:59

Cutline

(photo by Klaus Vedfelt/Getty Images)

Topic

Rotman School of Management

Subheadline

Researchers found that works featuring changes of fortune, or turning points, were more popular and received better audience reviews

Writers and scholars have long debated what makes for a great story, but Samsun Knight wanted to see whether there was a way to empirically determine which stories will be snore fests and which will leave audiences hungry for more.

Using a scientist’s tools, the novelist and economist found that “narrative reversals,” or peripeteias, were the key factor – lots of them and the bigger the better.

Samsun Knight (supplied image)

Commonly known as changes of fortune or turning points, where characters’ fortunes swing from good to bad and vice versa, Knight and his colleagues found that stories rich in these mechanisms boosted popularity and engagement with audiences through a range of media, from television to crowdfunding pitches.

“The best-written stories were always either ‘building up’ a current reversal, or introducing a new plot point,” says Knight, an assistant professor of marketing at the ��߲ݴ�ý’s Rotman School of Management.

“In our analysis, the best writers were those that were able to maintain both many plot points and strong build-up for each plot point across the course of the narrative.”

The research, co-authored with Matthew D. Rocklage and Yakov Bart of Boston’s Northeastern University, was recently published in the journal Science Advances.

For the study, the researchers analyzed nearly 30,000 television shows, movies, novels, and crowdfunding pitches using computational linguistics, a blend of computer science and language analysis. The approach allowed them to quantify not only the number of a reversals in a text but also their degree or intensity by assigning numerical values to words based on how positive or negative they were.

Movies and television shows with more and bigger reversals were better rated on the popular ratings site IMDb. Books with the most and biggest reversals were downloaded more than twice as often as books with the fewest reversals from the free online library Project Gutenberg. And GoFundMe pitches with more and larger reversals were as much as 39 per cent more likely to hit their fundraising goals.

The Greek philosopher Aristotle was the first to identify peripeteia as a key feature of a good story, with Oedipus Rex serving as a classic example. Other thinkers have since added their ideas, including American playwright and dramaturg Leon Katz, whose scholarship particularly inspired Knight’s research.

“[Katz] described the reversal as the basic unit of narrative – just as a sentence is the basic unit of a paragraph, or the syllogism is the basic unit of a logical proof,” Knight says.

In addition to helping psychologists understand how narrative works to educate, inform and inspire people, the findings may also benefit storytellers of all kinds.

“Hopefully our research can help build a pedagogy for writers that allows them to rely on the accumulated knowledge of Aristotle et al. without having to reinvent the wheel on their own every time,” says Knight.

That includes himself. With another novel on the way, he was recently working on a chapter with a big reveal.

“I realized that this drop might hit harder if I gave the character more positive moments before pulling the rug out from under them.”

Researchers' lab technique could speed forensic analysis in sexual assault cases

Christopher.Sorensen — Tue, 17 Sep 2024 14:43:28 +0000

Researchers' lab technique could speed forensic analysis in sexual assault cases

Christopher.Sorensen Tue, 09/17/2024 - 10:43

Cutline

(photo by Science Photo Library/Getty Images)

Chris Sasaki

Topic

Centre for Research and Applications in Fluidic Technologies

Donnelly Centre for Cellular & Biomolecular Research

Chemistry

Faculty of Arts & Science

U of T Mississauga

A team of researchers has developed a new approach to analyzing DNA evidence in sexual assault cases – one that could reduce lengthy delays in the processing of evidence.

While there are almost half a million sexual assaults in Canada every year, many more go unreported because victims are reluctant to come forward.

One of the reasons cited by victims is that analysis of forensic evidence is too slow.

Mohamed Elsayed (supplied image)

“For this research, we read reports and surveys that asked victims why they weren’t reporting assaults,” says the study’s lead author Mohamed Elsayed, who worked on the project as part of his PhD in biomedical engineering at the ��߲ݴ�ý. “And the most common answer was that they didn't have confidence in the justice system – and that lack of confidence was partly because of how long the process takes.”

Elsayed, now a post-doctoral researcher in the department of chemistry in the Faculty of Arts & Science, co-authored the study with, among others, Leticia Bodo, a master’s student in the department of chemistry, and Aaron Wheeler, a professor in the department of chemistry, the Institute of Biomedical Engineering and the Centre for Research and Applications in Fluidic Technologies, a U of T institutional strategic initiative.

All three researchers are also affiliated with the Donnelly Centre for Cellular and Biomolecular Research.

Processing forensic evidence in sexual assault cases is a technical, multi-step process that involves collecting DNA evidence and sending it to a well-equipped forensic laboratory for analysis by a skilled technician. Once there, the sample is first processed to isolate the assailant’s DNA from the victim’s so the assailant’s DNA can then be analyzed and used to identify a suspect.

The entire process can take days, weeks or longer. Most of that time is taken up with transporting the evidence to the lab, where its analysis can be further delayed depending on how many other cases are being investigated.

To speed things up, researchers focused on the first step: separating two individuals’ DNA from a single sample. At present, this is usually done manually by trained and experienced experts.

Elsayed and his collaborators, by contrast, developed a process called ’differential digestion” using digital microfluidics that helped simplify the overall process and reduce the number of manual steps needed to isolate the assailant’s DNA from 13 to five. “Also, because micro-fluidic processes tend to be faster, we expect that one of the eventual benefits will be shortening the overall time needed,” says Elsayed.

What’s more, the new approach could lead to a mobile solution that no longer requires a lab. For example, testing could be done at a hospital, circumventing the lab’s queue.

The new technique, described in a paper published in the journal Advanced Science, is compatible with the technology known as Rapid DNA analysis that is already in use for the second step of identifying an individual from their DNA. The study’s authors, which included researchers from U of T Mississauga’s forensic science program, say the long-term goal is to integrate the two technologies to make the process even more streamlined.

While there remain several challenges to deploying the new technique, Elsayed says he is confident they can be overcome and has turned his efforts toward making it widely accessible and commercially viable.

“Our plan is to develop an instrument that will do in five minutes what currently takes 45,” says Elsayed. “And to run many more samples than previously. Once we do that, the next step would be to introduce the technology to forensic labs and hospitals.

“It will take years, but the potential is very exciting.”

The research was supported by the ANDE Corporation and NSERC Alliance Society.

"I’m grateful to NSERC for having the foresight to establish the ‘Alliance Society’ program which has a mission to ‘address a societal challenge that will result in new natural sciences and engineering knowledge and societal impact,” Wheeler says.

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Forensic Science

Researchers develop new method for delivering RNA and drugs into cells

Christopher.Sorensen — Mon, 16 Sep 2024 15:02:15 +0000

Researchers develop new method for delivering RNA and drugs into cells

Christopher.Sorensen Mon, 09/16/2024 - 11:02

Cutline

PhD candidate Kai Slaughter, left, and University Professor Molly Shoichet are exploring how ionizable drugs can be used to co-formulate small interfering RNA (siRNA) for more effective intracellular delivery (supplied images)

Qin Dai

Topic

Princess Margaret Cancer Centre

Donnelly Centre for Cellular & Biomolecular Research

Faculty of Applied Science & Engineering

University Health Network

Subheadline

"This could be a game-changer for treating complex conditions where targeting multiple pathways is beneficial, such as cancer and viral infections"

Researchers at the ��߲ݴ�ý and its hospital partners have developed a method for co-delivering therapeutic RNA and potent drugs directly into cells, potentially leading to a more effective treatment of diseases.

The research, published recently in the journal Advanced Materials, explores how ionizable drugs can be used to co-formulate small interfering RNA (siRNA) for more effective intracellular delivery.

The team – including Molly Shoichet, the study’s corresponding author and a University Professor in U of T’s department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering – specifically targeted drug-resistant cells with the delivery of a relevant siRNA. The siRNA was discovered study co-author and collaborator David Cescon, a clinician scientist at the Princess Margaret Cancer Centre, University Health Network, and an associate professor in U of T’s Temerity Faculty of Medicine.

“We found that our co-formulation method not only potently delivered siRNA to cells but also simultaneously delivered active ionizable drugs,” said research lead author Kai Slaughter, a PhD candidate in Shoichet’s lab.

“This could be a game-changer for treating complex conditions where targeting multiple pathways is beneficial, such as cancer and viral infections.”

siRNA is a powerful tool in medicine, capable of silencing specific genes responsible for disease, but delivering these molecules into cells without degradation remains a significant challenge. While recent innovations in ionizable lipid design have led to efficiency improvements, traditional nanoparticle formulations are limited in the amount of small molecule drugs they can carry.

When therapeutic formulations are absorbed by cells, small molecule drugs and siRNA are often trapped in small compartments called endosomes, preventing them from reaching their target destination and reducing their effectiveness.

The research team discovered that combining siRNA with ionizable drugs – compounds that change their charge based on pH levels – enhances the stability and delivery efficiency of siRNA inside cells, helping both the siRNA and drug escape the endosome and more effectively reach their destination. This novel method utilizes the protective properties of lipids to safeguard siRNA during its journey through the body and ensure the release of RNA and the drug together within the target cells.

“One of the biggest hurdles in siRNA therapy has been getting these molecules to where they need to go without losing their potency,” Shoichet says.

“Our approach using ionizable drugs as carriers marks a significant step forward in overcoming this barrier, while also showing how drugs and RNA can be delivered together in the same nanoparticle formulation.”

Caution needed when drawing links between improving symptoms and unproven remedies: Study

Christopher.Sorensen — Fri, 06 Sep 2024 16:03:17 +0000

Caution needed when drawing links between improving symptoms and unproven remedies: Study

Christopher.Sorensen Fri, 09/06/2024 - 12:03

Cutline

(photo by Oleksandra Yagello/Getty Images)

Sunnybrook Staff

Topic

Sunnybrook Health Sciences Centre

Institute of Health Policy Management and Evaluation

Dalla Lana School of Public Health

Subheadline

"Post-hoc bias can play tricks on patients that can eventually lead to serious disappointments – and for health-care workers, it can ultimately lead to shortfalls in care"

People tend to continue with unproven treatments even if there’s no evidence to suggest an initial marginal improvement in symptoms is anything more than a potential coincidence, a new study has found.

"I've noticed many of my patients take unnecessary vitamins, pills or alternative remedies with little evidence to inform their choice, leading to a lot of distraction, wishful thinking and wasted money,” says senior study author Donald Redelmeier, a staff internist and senior scientist at Sunnybrook Health Sciences Centre, and professor in the department of medicine in the ��߲ݴ�ý’s Temerty Faculty of Medicine.

“Perhaps even more concerning is a false belief that leads to a missed diagnosis that later becomes incurable.”

The study, published in the journal JAMA Network Open, explores “post-hoc bias” – a tendency in reasoning that causes many patients to continue taking dubious or unreliable treatments. The bias encourages a popular misconception: that because one action preceded another later event, the first must have caused the second since it occurred in sequence.

But medical science, the researchers note, stresses that the order of two events does not prove a cause-and-effect since coincidences are frequent. The implication for medical care is that a patient who improved after a treatment is not necessarily a patient who improved because of the treatment.

Instead, other potential explanations include withdrawal from an adverse activity, added rest or the body’s own healing powers.

To test bias across a variety of clinical cases, the researchers ran multiple experiments using hypothetical clinical scenarios administered by a randomized survey of pharmacists and members of the community.

The scenarios described a patient with fatigue or another vague symptom who feels a bit better after trying a vitamin, shampoo, sugar pill or other treatment.

“We found that most respondents suggested continuing the treatment indefinitely even though the change in symptoms might be pure random chance," says Redelmeier, who is also affiliated ICES and the Institute for Health Policy, Management and Evaluation in U of T’s Dalla Lana School of Public Health.

"The post-hoc bias can play tricks on patients that can eventually lead to serious disappointments – and for health-care workers, it can ultimately lead to shortfalls in care."

While attributing an initial improvement in – or lack of – symptoms to a treatment is a quick and intuitive approach, the researchers say the study reinforces the need for both patients and clinicians to be cautious when drawing conclusions.

“An awareness of post-hoc bias will not make it disappear, however we suggest patients and clinicians need to think twice and stay mindful of alternative explanations.”

The study was supported by the Alfred P. Sloan Foundation, a Canada Research Chair in Medical Decision Sciences, Canadian Institutes of Health Research, the PSI Foundation of Ontario and the National Science Foundation.

This story was originally posted at Sunnybrook Research Institute

Research team explores next-gen vaccines to guard against sexually transmitted infections

Christopher.Sorensen — Wed, 04 Sep 2024 16:07:53 +0000

Research team explores next-gen vaccines to guard against sexually transmitted infections

Christopher.Sorensen Wed, 09/04/2024 - 12:07

Cutline

Aereas Aung, an assistant professor in the Institute of Biomedical Engineering , is developing new tools to study and manipulate immune cells and their reaction to vaccines (photo by Tim Fraser)

Qin Dai

Topic

Faculty of Applied Science & Engineering

Connaught Fund

Vaccines

Subheadline

"This work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases”

A research team from the ��߲ݴ�ý is creating a new generation of vaccines that aims to overcome key hurdles faced by some existing formulations.

For example, a common shortcoming of many traditional vaccines is that they can’t produce antibodies in tissues where sexually transmitted infections (STIs) often enter the body.

“Most current vaccines fail to produce sufficient antibodies within mucosal tissues, leaving a significant gap in our defense against sexually transmitted infections,” says Aereas Aung, an assistant professor at the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering who is leading the research effort.

“Our goal is to develop a novel strategy that leverages the strengths of parenteral vaccination while also targeting the mucosal immune system.”

Normally vaccines are injected parenterally, meaning it is injected into or under the skin, into the muscle or directly into the bloodstream. The vaccine then travels to lymph nodes, which are small glands that help produce antibodies. Mucosal tissues in the cervix and rectum present a unique challenge since the mucus in these areas can break down the vaccine quickly and wash it away, making it difficult to reach the lymph nodes and be effective.

Aung’s research proposes fusing a protein carrier to the disease antigens, allowing it to reach distant mucosal lymph nodes after injection.

“We aim to incorporate potent immunostimulatory components into our antigen construct, optimizing its distribution and enhancing mucosal antibody responses,” says Aung.

“If successful, this work could lay the foundation for more effective vaccines that curb the spread of STIs, particularly in marginalized communities disproportionately affected by these diseases.”

Aung’s project is one of 51 U of T faculty members whose work is being supported by the Connaught New Researcher Awards in the most recent round – and one of eight at U of T Engineering. The award helps early-career faculty members establish their research programs.

The other U of T Engineering researchers whose projects are supported by the award are: 

Mohammed Basheer, department of civil and mineral engineering – Integrated hydrological-statistical method and tool for landslide susceptibility mapping in a changing climate
Daniel Franklin, Institute of Biomedical Engineering – Development of equitable pulse oximeters
Sarah Haines, department of civil and mineral engineering – Open Plenums & Indoor Environments (OPEN): Evaluating the impact of return air systems on indoor environmental quality
Mark Jeffrey, Edward S. Rogers Sr. department of electrical and computer engineering – Productively surmounting the memory wall with task parallelism
Caitlin Maikawa, Institute of Biomedical Engineering – Affinity-directed dynamic polymer materials for biomarker sensing
Mohamad Moosavi, department of chemical engineering and applied chemistry – Learning the Language of Metal-Organic Frameworks Topology
Cindy Rottmann, Institute for Studies in Transdisciplinary Engineering Education and Practice (ISTEP) – But I could be fired! How early career engineers hold the public paramount from organizationally subordinate locations

Virtual and augmented reality can temporarily change the way people perceive distances: Study

Christopher.Sorensen — Fri, 30 Aug 2024 17:23:24 +0000

Virtual and augmented reality can temporarily change the way people perceive distances: Study

Christopher.Sorensen Fri, 08/30/2024 - 13:23

Cutline

U of T researchers found that people moved differently in virtual reality and augmented reality, and that these changes led to temporary movement errors in the real world (photo by D-BASE/Getty Images)

Jelena Damjanovic

Topic

Faculty of Kinesiology & Physical Education

Virtual Reality

Subheadline

'We wanted to understand if the way our brains and bodies adapt to these digital environments changes how accurately we can move and interact with real objects"

Researchers at the ��߲ݴ�ý have found that using virtual and augmented reality (VR and AR) can temporarily change the way people perceive and interact with the real world – with potential implications for the growing number of industries that use these technologies for training purposes.

The study, published recently in the journal Scientific Reports, not only found that people moved differently in VR and AR, but that these changes led to temporary errors in movement in the real world. In particular, participants who used VR tended to undershoot their targets by not reaching far enough, while those who used AR tended to overshoot their targets by reaching too far.

This effect was noticeable immediately after using VR or AR, but gradually disappeared as participants readjusted to real-world conditions.

“Our study explored how using mixed reality (MR) technologies, like virtual reality and augmented reality, affects our ability to perform everyday physical tasks once we return to the real world,” says Xiaoye Michael Wang, a research associate in the Faculty of Kinesiology & Physical Education who co-authored the study with Professor Tim Welsh.

“Specifically, we wanted to understand if the way our brains and bodies adapt to these digital environments changes how accurately we can move and interact with real objects after using VR and AR.”

Research associate Xiaoye Michael Wang fits a VR display onto study participant Colin Dolynski (photo by Molly Brillinger)

The researchers say they were surprised by two findings: first, that movement patterns in VR and AR transfer to real-world movements; and second, by how quickly the effects of AR wore off compared to VR, with study participants readjusting to real-world conditions faster after using AR.

The difference between VR and AR, they suggest, might be because people in AR can still see and interact with their actual surroundings, which helps them maintain a more accurate sense of depth and distance.

“These findings are crucial because they highlight a potential challenge in transferring skills learned in VR or AR to the real world,” says Welsh. “As more industries and training programs adopt these technologies for skill development, it's important to understand how they might affect real-world performance.

“For example, this could be relevant for training surgeons, pilots or even everyday skills like driving. Knowing the limitations and effects of VR and AR helps ensure these technologies are used effectively and safely.”

The researchers will next be exploring how different types of VR and AR experiences, like those involving more complex or immersive scenarios, affect real-world performance. They’re also interested in seeing how training duration and individual differences such as prior experience with these technologies, influence adaptation and readjustment.

“This research will help us better understand how to design VR and AR systems that minimize negative after-effects and maximize their potential for training and skill development,” Wang says.

U of T researchers integrate crucial immune cells onto heart-on-a-chip platform

Christopher.Sorensen — Fri, 23 Aug 2024 12:56:51 +0000

U of T researchers integrate crucial immune cells onto heart-on-a-chip platform

Christopher.Sorensen Fri, 08/23/2024 - 08:56

Cutline

L-R: U of T post-doctoral fellow Shira Landau, PhD alum Yimu Zhao and Professor Milica Radisic are three of the primary authors of a study that could lead to advancements in the creation of more stable and functional heart tissues (supplied images)

Qin Dai

Topic

Donnelly Centre for Cellular & Biomolecular Research

Toronto General Hospital

Faculty of Applied Science & Engineering

University Health Network

Subheadline

The immune cells, known as primitive macrophages, were found to enhance heart tissue function and vessel stability

Researchers at the ��߲ݴ�ý have discovered a novel method for incorporating primitive macrophages – crucial immune cells – into heart-on-a-chip technology, in a potentially transformative step forward in drug testing and heart disease modeling.

In a study published in Cell Stem Cell, an interdisciplinary team of scientists describe how they integrated the macrophages – which were derived from human stem cells and resemble those found in the early stages of heart development – onto the platforms. These macrophages are known to have remarkable abilities in promoting vascularization and enhancing tissue stability.

Corresponding author Milica Radisic, a senior scientist in the University Health Network's Toronto General Hospital Research Institute and professor in the Institute of Biomedical Engineering at U of T’s Faculty of Applied Science & Engineering, says the approach promises to enhance the functionality and stability of engineered heart tissues.

“We demonstrated here that stable vascularization of a heart tissue in vitro requires contributions from immune cells, specifically macrophages. We followed a biomimetic approach, re-establishing the key constituents of a cardiac niche,” says Radisic, who holds a Canada Research Chair in Functional Cardiovascular Tissue Engineering

“By combining cardiomyocytes, stromal cells, endothelial cells and macrophages, we enabled appropriate cell-to-cell crosstalk such as in the native heart muscle.”

Professor Milica Radisic's research team have worked on developing a miniaturized version of cardiac tissue on heart-on-a-chip platforms for a decade (photo by Nick Iwanyshyn)

A major challenge in creating bioengineered heart tissue is achieving a stable and functional network of blood vessels. Traditional methods have struggled to maintain these vascular networks over extended periods, limiting their effectiveness for long-term studies and applications.

In their study, researchers demonstrated that the primitive macrophages could create stable, perfusable microvascular networks within the cardiac tissue, a feat that had previously been difficult to achieve.

Furthermore, the macrophages helped reduce tissue damage by mitigating cytotoxic effects, thereby improving the overall health and functionality of the engineered tissues.

“The inclusion of primitive macrophages significantly improved the function of cardiac tissues, making them more stable and effective for longer periods,” says Shira Landau, a post-doctoral fellow in Radisic’s lab and one of the study’s lead authors.

The breakthrough has far-reaching implications for the field of cardiac research. By enabling the creation of more stable and functional heart tissues, researchers can better study heart diseases and test new drugs in a controlled environment.

Researchers say this technology could lead to more accurate disease models and more effective treatments for heart conditions.

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle — Tue, 20 Aug 2024 16:17:45 +0000

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle Tue, 08/20/2024 - 12:17

Cutline

The "SynNeurGe" classification system for Parkinson's disease, proposed by researchers led by Professor Anthony Lang of the University Health Network and U of T, is based on three key biomarkers (photo by FG Trade/Getty Images)

Eileen Hoftyzer

Topic

Department of Medicine

Tanz Centre for Research in Neurodegenerative Diseases

Parkinson's

University Health Network

Subheadline

The classification system could enable advancements in the development of tailored treatments for Parkinson's disease

A team of researchers led by Anthony Lang of the University Health Network and the ��߲ݴ�ý have proposed a novel classification system for Parkinson’s disease that considers biological features and not just clinical symptoms.

The "SynNeurGe" system, described by Lang and collaborators in a paper published in The Lancet Neurology, classifies Parkinson’s disease based on three biomarkers: presence or absence of misfolded alpha synuclein protein, which is believed to cause or contribute to the underlying neurodegeneration; evidence of neurodegeneration using imaging techniques; and presence of gene variants that increase disease risk.

The researchers argue that such a classification system is necessary to advance the development of tailored treatments for Parkinson’s disease.

Professor Anthony Lang (supplied image)

“This is a complex group of disorders that may cause similar symptoms, but biologically they're very different,” says Lang, a senior scientist and Lily Safra Chair in Movement Disorders at UHN and a professor in the department of medicine and the Tanz Centre for Research in Neurodegenerative Disease at U of T’s Temerty Faculty of Medicine, where he holds the Jack Clark Chair for Parkinson’s Disease Research

“If we cannot find ways to subdivide patients biologically, then applying a therapy designed to affect one biological pathway may not be effective in another group of patients that doesn't have that same pathway involved – and we won’t really have precision or personalized medicine for Parkinson’s disease.”

Currently, Parkinson’s disease is classified based on clinical presentation and symptoms, but the disease can affect the brain for years, possibly even decades, before symptoms appear. For future therapies to treat the underlying disease rather than just the symptoms, patients will need early intervention and treatments tailored to the biological features of the disease, researchers say.

Similar approaches are being used for other diseases – cancer treatments vary not only by the location of tumors but also their molecular features, and the development of drugs for Alzheimer’s disease is increasingly guided by the specific biological mechanisms involved in the disease.

The SynNeurGe classification system, while based on the three key biomarkers, also considers whether clinical features are present. The different combinations of biomarkers classify the disease into various sub-types.

Lang and co-authors note that such a classification should only be used for research at present, although it will almost certainly have clinical applications.

“Eventually we will see a biological approach influencing clinical care, particularly when we finally have effective disease-modifying therapies,” says Lang. “We currently don’t know how important these biomarkers actually are.

"We need large-scale prospective studies of biomarkers, imaging and clinical features to interpret the results, give patients accurate information about their diagnosis and provide appropriate treatment.”

Lang’s team plans to start conducting such studies of cerebrospinal fluid, skin and blood to look for biomarkers of different sub-types of Parkinson’s disease that will help inform the classification system and the development of tailored therapies.

“Now is the time to think about these diseases not solely based on their clinical manifestations, but to look at the biology and try to separate different biological subtypes so we can ultimately improve treatment for this disease,” Lang says.

Professor Graham Collingridge, director of the Tanz Centre, says Lang and his team’s “landmark paper” is poised to have a significant impact on clinical practice around Parkinson's. “I am delighted that our researchers have played such a key role in this important biological classification,” Collingridge says.

Lang says research by Tanz Centre scholars has contributed significantly to the body of knowledge used to develop the proposed biological classification.

For example, Professor Ekaterina Rogaeva’s research on the genetics and epigenetics of Parkinson’s disease has shown that multiple genes and environments can influence Parkinson’s risk, highlighting the need to tailor therapies based on a patient’s genetic makeup.

Other researchers – including Anurag Tandon, Joel Watts, Martin Ingelsson and Gabor Kovacs – have been studying the role of misfolded alpha synuclein in neurodegeneration as well as cases of Parkinson’s disease where alpha synuclein is absent – which informed how Lang’s team included the protein in the classification.

U of T researchers develop AI model to predict 'very dynamic' peptide structures

Christopher.Sorensen — Thu, 15 Aug 2024 12:54:41 +0000

U of T researchers develop AI model to predict 'very dynamic' peptide structures

Christopher.Sorensen Thu, 08/15/2024 - 08:54

Cutline

PhD Graduate Osama Abdin and Professor Philip M. Kim developed a deep-learning model that can predict all possible shapes of peptides, which are are of keen interest to researchers who are developing therapeutics (supplied image)

Anika Hazra

Topic

Donnelly Centre for Cellular & Biomolecular Research

Alumni

Artificial Intelligence

Computer Science