Deep Immune Profiling Shows Significant Immune Activation in Children with MIS-C (Medicine)

CHOP/Penn study shows T cell activation in children with MIS-C more similar to adults with severe COVID-19

Taking the first deep dive into how the immune system is behaving in patients with multisystem inflammatory syndrome in children (MIS-C), researchers at Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania have found that children with this condition have highly activated immune systems that, in many ways, are more similar to those of adults with severe COVID-19.

The results, published today in Science Immunology, show that better understanding the immune activation in patients with MIS-C could not only help better treat those patients but also improve treatment for adults with severe COVID-19.

“This study shows that children with MIS-C are tremendously immune activated, particularly when it comes to CD8 T cells, but that this activation subsides once patients begin to improve clinically,” said Laura Vella, MD, PhD, attending physician in the Division of Infectious Diseases at CHOP and first author of the study. “Our findings provide a broad immunologic foundation for understanding pathogenesis and recovery in this novel SARS-CoV-2-associated inflammatory syndrome, with potential implications for adult disease.”

Pediatricians first recognized MIS-C in April 2020, when pediatric patients began presenting with symptoms involving hyperinflammation, including fever, gastrointestinal distress and cardiogenic shock. The syndrome, thought to be a post-infectious complication of SARS-CoV-2 infection, has similarities in clinical presentation to Kawasaki disease, especially the vascular involvement, but it differs from Kawasaki disease in key ways, including unique clinical, inflammatory, and autoantibody signatures. The syndrome also lacks the respiratory complications typical of adult and pediatric COVID-19. However, until this point, the immunologic features driving MIS-C remained poorly understood.

To better understand the immunology behind MIS-C, the researchers collected blood samples from patients admitted to CHOP with COVID-19 or MIS-C between April and June of 2020. They analyzed more than 200 immune parameters, including serologic and plasma cytokine data, and compared these data with samples from adult COVID-19 patients, recovered adult COVID-19 subjects, and healthy adults.

The researchers found that children with MIS-C had highly elevated T cells, particularly CD8 T cells and a highly activated vascular patrolling CD8 T cell subset. These vascular patrolling CD8 T cells have a proposed role in the control of persisting or reactivating viral infection and have also been implicated in cardiovascular disease, which could have relevance to the vascular symptoms observed in these patients. The researchers found patients with MIS-C, who all had high vascular patrolling CD8 T cells, also required vasoactive support, had elevated D-dimer, and had decreased platelets. The elevation of CD8 T cells far exceeded what the researchers observed in pediatric patients with acute COVID-19 and most adults with COVID-19, but the level of CD8 T cells dropped in MIS-C patients in conjunction with clinical improvement.

The study also highlighted a skewed B cell response in patients with MIS-C compared to acute pediatric COVID-19 and resolved adult disease. Patients with MIS-C are almost universally seropositive for SARS-CoV-2, meaning enough time had passed since infection for an antiviral antibody to develop and be detected. Pediatric and adult patients with acute COVID-19 were not seropositive, consistent with the belief that that MIS-C is a delayed event following SARS-CoV-2 infection. Yet despite MIS-C being a delayed event, the researchers found that MIS-C patients had elevated plasmablasts, or immature plasma B cells, whereas plasmablasts in adults who recover from COVID-19 return to baseline two to three weeks after symptoms resolve, although a subset of hospitalized adult patients with COVID-19 did have a sustained elevation of plasmablasts.

The researchers proposed three possible drivers of the immune pathogenesis in MIS-C: (1) continued activation of adaptive immune responses, driven by persisting SARS-CoV-2 antigen; (2) an additional trigger, such as the virus localizing to a new tissue type or a secondary infection, occurring two to three weeks after the initial infection with SARS-CoV-2; or (3) an autoimmune response. More research is needed to investigate these potential scenarios.

“SARS-CoV2 infection can lead to a broad spectrum of clinical and immunological outcomes,” said E. John Wherry, PhD, director of the Penn Medicine Institute for Immunology and senior author of the study. “The use of an ‘Immune Health’ profiling approach for pediatric COVID-19 patients identified distinct features of the pediatric MIS-C presentation of disease. The insights gained by studying those patients may reveal new therapeutic opportunities not only for pediatric COVID-19 patients, but adult COVID-19 patients as well.”

The research was supported by the National Institutes of Health, as well as the University of Pennsylvania Institute for Immunology Glick COVID-19 research award, the Allen Institute for Immunology, a Cancer Research Institute-Mark Foundation Fellowship, the Leukemia and Lymphoma Society, Alex’s Lemonade Stand Foundation for Childhood Cancer, and the CHOP Frontiers Program Immune Dysregulation Team.


Reference: Vella et al. “Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19,” Science Immunology, online March 2, 2021, DOI: 10.1126/sciimmunol.abf7570


Provided by Children’s Hospital of Philadelphia


About Children’s Hospital of Philadelphia: Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 595-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Vegan Diet Better for Weight Loss and Cholesterol Control than Mediterranean Diet (Food)

A vegan diet is more effective for weight loss than a Mediterranean diet, according to a groundbreaking new study that compared the diets head to head. The randomized crossover trial, which was published in Journal of the American College of Nutrition, found that a low-fat vegan diet has better outcomes for weight, body composition, insulin sensitivity, and cholesterol levels, compared with a Mediterranean diet. 

The study randomly assigned participants—who were overweight and had no history of diabetes—to a vegan diet or a Mediterranean diet in a 1:1 ratio. For 16 weeks, half of the participants started with a low-fat vegan diet that eliminated animal products and focused on fruits, vegetables, whole grains, and legumes. The other half started with the Mediterranean diet, which followed the PREDIMED protocol, which focuses on fruits, vegetables, legumes, fish, low-fat dairy, and extra virgin olive oil, while limiting or avoiding red meat and saturated fats. Neither group had a calorie limit, and participants did not change exercise or medication routines, unless directed by their personal doctors. As part of the crossover design, participants then went back to their baseline diets for a four-week washout period before switching to the opposite group for an additional 16 weeks.

The study found that within 16 weeks on each diet:

  • Participants lost an average of 6 kilograms (or about 13 pounds) on the vegan diet, compared with no mean change on the Mediterranean diet.
  • Participants lost 3.4 kg (about 7.5 pounds) more fat mass on the vegan diet. 
  • Participants saw a greater reduction in visceral fat by 315 cm3 on the vegan diet. 
  • The vegan diet decreased total and LDL cholesterol levels by 18.7 mg/dL and 15.3 mg/dL, respectively, while there were no significant cholesterol changes on the Mediterranean diet. 
  • Blood pressure decreased on both diets, but more on the Mediterranean diet (6.0 mm Hg, compared to 3.2 mmHg on the vegan diet).

“Previous studies have suggested that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but until now, their relative efficacy had not been compared in a randomized trial,” says study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. “We decided to test the diets head to head and found that a vegan diet is more effective for both improving health markers and boosting weight loss.”

The authors note that the vegan diet likely led to weight loss, because it was associated with a reduction in calorie intake, increase in fiber intake, decrease in fat consumption, and decrease in saturated fat consumption. 

“While many people think of the Mediterranean diet as one of the best ways to lose weight, the diet actually crashed and burned when we put it to the test,” says study author Neal Barnard, MD, president of the Physicians Committee. “In a randomized, controlled trial, the Mediterranean diet caused no weight loss at all. The problem seems to be the inclusion of fatty fish, dairy products, and oils. In contrast, a low-fat vegan diet caused significant and consistent weight loss.”

“If your goal is to lose weight or get healthy in 2021, choosing a plant-based diet is a great way to achieve your resolution,” adds Dr. Kahleova.


Reference: Neal D. Barnard, Jihad Alwarith, Emilie Rembert, Liz Brandon, Minh Nguyen, Andrea Goergen, Taylor Horne, Gabriel F. do Nascimento, Kundanika Lakkadi, Andrea Tura, Richard Holubkov & Hana Kahleova (2021) A Mediterranean Diet and Low-Fat Vegan Diet to Improve Body Weight and Cardiometabolic Risk Factors: A Randomized, Cross-over Trial, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2020.1869625


Provided by PCRM

How Long Earth Oxygen Will Sustain? (Planetary Science)

Ozaki and Reinhard in their recent paper, examined the timescale of oxygen-rich atmosphere on Earth by using a combined biogeochemistry and climate model. They found that Earth will lose its oxygen-rich atmosphere in 1. 08 ± 0.14 billion years (which is appx. 1 billion years). Their paper recently appeared in Journal Nature Geoscience.

They showed that future deoxygenation is an inevitable consequence of increasing solar fluxes, whereas its precise timing is modulated by the exchange flux of reducing power between the mantle and the ocean-atmosphere-crust system.

Fig. 1. Schematic model structure. Boxes denote reservoirs, whereas arrows denote flux terms. The model tracks the major reservoirs and transfer fluxes within the surface carbon (C), sulphur (S), oxygen (O), and phosphorus (P) cycles, along with a comprehensive treatment of ocean biogeochemistry, and long-term transfers between the crust-ocean-atmosphere system and the mantle. DOA = degree of anoxia.

That is, around 1 billion years from now on, sun will grew hotter, releasing more energy, carbon dioxide levels in Earth’s atmosphere will begin to drop due to the gas absorbing the heat and breaking down. The ozone layer would also be burned away. Then, as carbon dioxide levels fall, plant life will begin to suffer, resulting in reduced production of oxygen.

Over a period of just 10,000, years, CO2 levels will drop so much that plant life would go extinct. Without plant life, land- and sea-dwelling creatures would soon go extinct, as well, due to the lack of a breathable atmosphere. Meanwhile, the model results also showed increasing levels of methane entering the atmosphere, speeding the demise of creatures needing oxygen to breathe. The result, according to the model, would be a planet without life, save for tiny anaerobic creatures such as bacteria—conditions very similar to Earth prior to the evolution of plants and animals.

But, it is also important to note that there are multiple biogeochemical and climate processes that are not considered in their model that may play a role in constraining the future lifespan of Earth’s biosphere and the timing/mode of transition to more reducing atmospheric conditions. In particular, “reverse weathering” (the formation of authigenic silicates in marine sediments, resulting in net CO2 release to the ocean-atmosphere system) could potentially extend the lifespan of oxygenated atmospheric conditions under certain scenarios by prolonging the timescale over which atmospheric CO2 is above the levels expected to result in CO2 limitation of the photosynthetic biosphere.

In addition, they also hypothesized that haze-induced climate cooling could potentially act as a brake on the overall magnitude of atmospheric deoxygenation, or result in the inception of oxygenation/deoxygenation cycles during Earth’s terminal habitability.

Their results have important implications for the search for life on Earth-like planets beyond our solar system (e.g., habitable planets with abundant liquid water at the surface, exposed silicate crust, and a biosphere with oxygenic photosynthesis). According to authors, there is a need for robust atmospheric biosignatures applicable to weakly oxygenated and anoxic exoplanet atmospheres.


Reference: Ozaki, K., Reinhard, C.T. The future lifespan of Earth’s oxygenated atmosphere. Nat. Geosci. (2021). https://www.nature.com/articles/s41561-021-00693-5 https://doi.org/10.1038/s41561-021-00693-5


Copyright of this article totally belongs to our author S. Aman. One is allowed to reuse it only by giving proper credit either to him or to us

Astronomers Discovered 3 Rapidly Rotating Ultra-Cool Dwarfs (Planetary Science)

Tannock and colleagues presented the discovery of rapid photometric variability in three ultra-cool dwarfs from long-duration monitoring with the Spitzer Space Telescope. The T7, L3.5, and L8 dwarfs have the shortest photometric periods known to date: 1.080 h, 1.14 h, and 1.23 h, respectively. Their study recently appeared in Journal Zenodo.

They compared the near-infrared spectra to photospheric models to determine the objects’ fundamental parameters and radial velocities (RVs) (which is shown in Table 1 below).

Table 1. Physical Parameters for the Three L and T Dwarfs © Tannock et al.

All three objects are likely substellar. At a spectral type of L3.5, 2MASS J0407+1546 is the warmest, have fairly cloudy atmosphere and potentially most massive among their three L and T dwarfs. While, based on T7 spectral type, researchers expect that 2MASS J0348+6022 have relatively clear and cloudless atmosphere and that of 2MASS J1219+3128 have dusty atmosphere. Their rapid rotations and Hα emissions may well indicate the presence of an aurora. Based on radio detections of three L and T dwarfs with short (1.5 h–2.2 h) rotation periods, rapid rotation is key to powering auroral emissions via the electron synchrotron maser instability.

They are excellent candidates for seeking auroral radio emission, which has been linked to rapid rotation in ultra-cool dwarfs.

— told tannock, lead author of the study.

They confirmed the rapid rotation through moderate resolution infrared spectroscopy that reveals projected rotational velocities of 103.5 km s¯1 for 2MASS J0348−6022 (T7), 79.0 km s¯1 for 2MASS J1219+3128 (L8) and 82.6 km s¯1 for 2MASS J0407+1546 (L3.5), these are among the most rapidly spinning ultra-cool dwarfs known to date. They also found that the objects have oblateness factors of between 5% and 8%, which also makes them the most oblate field ultra-cool dwarfs known to date and ranks them among the best targets for seeking net optical or infrared polarization.

They also considered the role of the centrifugal acceleration on surface gravity, and found that while the effect can be significant, at .0.1 dex in surface gravity it can be difficult to discern with current photospheric models.

Including this paper, 78 L-, T-, and Y-dwarf rotation periods have now been measured. The clustering of the shortest rotation periods near 1 h suggests that brown dwarfs are unlikely to spin much faster.

Featured image: Pixel phase-corrected flux at 3.6 and 4.5 as a function of centroid position in both the x- and y-directions. The centroids are measured relative to the average centroids across all exposures. The Pearson correlation coefficients (r) are given in each panel and they found that there is no correlation between the flux and centroid positions on the detector. They concluded that there is no residual periodic effect on the photometry after correcting for Spitzer’s pointing wobble. © Tannock et al.


Reference: Tannock, Megan E., Metchev, Stanimir, Heinze, Aren, Miles-Páez, Paulo, Gagné, Jonathan, Burgasser, Adam, … Plavchan, Peter. (2021). Weather on Other Worlds. V. The Three Most Rapidly Rotating Ultra-Cool Dwarfs. Presented at the The 20.5th Cambridge Workshop on Cool Stars, Stellar Systems, and the Sun (CS20.5), virtually anywhere: Zenodo. https://zenodo.org/record/4560684 http://doi.org/10.5281/zenodo.4560684


Copyright of this article totally belongs to our author S. Aman. One is allowed to reuse it only by giving proper credit either to him or to us

New Copolymer Binder To Extend the Life of Lithium Ion Batteries (Material Science)

Scientists develop a novel binder material that protects the graphite anode of Li-ion batteries from degradation even after 1700 cycles

Anyone who has owned a smartphone for over a year is most likely aware that its built-in lithium (Li)-ion battery does not hold as much charge as when the device was new. The degradation of Li-ion batteries is a serious issue that greatly limits the useful life of portable electronic devices, indirectly causing huge amounts of pollution and economic losses. In addition to this, the fact that Li-ion batteries are not very durable is a massive roadblock for the market of electric vehicles and renewable energy harvesting. Considering the severity of these issues, it is no surprise that researchers have been actively seeking ways to improve upon the state-of-the-art designs of Li-ion batteries.

One of the major causes for the drop in capacity over time in Li-ion batteries is the degradation of the widely used graphite anodes–the negative terminals in batteries. The anode, together with the cathode (or the positive terminal) and the electrolyte (or the medium that carries the charge between two terminals), provide an environment where the electrochemical reactions for the charging and discharging of the battery can take place. However, graphite requires a binder to prevent it from falling apart with use. The most widely adopted binder today, poly(vinylidene fluoride) (PVDF), has a series of drawbacks that render it far from an ideal material.

To tackle these issues, a team of researchers from Japan Advanced Institute of Science and Technology (JAIST) are investigating a new type of binder made from a bis-imino-acenaphthenequinone-paraphenylene (BP) copolymer. Their latest study, published in ACS Applied Energy Materials, was led by Professor Noriyoshi Matsumi and also involved Professor Tatsuo Kaneko, Senior Lecturer Rajashekar Badam, PhD student Agman Gupta, and former postdoctoral fellow Aniruddha Nag.

So, in what regards does the BP copolymer outperform the conventional PVDF binder for graphite anodes? First, the BP binder offers significantly better mechanical stability and adherence to the anode. This comes in part from the so-called π-π interactions between the bis-imino-acenaphthenequinone groups and graphite, and also from the good adherence of the copolymer’s ligands to the copper current collector of the battery. Secondly, not only is the BP copolymer much more conductive than PVDF, it also forms a thinner conductive solid electrolyte interface with less resistance. Thirdly, the BP copolymer does not react easily with the electrolyte, which also greatly prevents its degradation.

All these advantages combined led to some serious performance improvements, as the researchers demonstrated through experimental measurements. “Whereas a half-cell using PVDF as a binder exhibited only 65% of its original capacity after about 500 charge-discharge cycles, the half-cell using the BP copolymer as a binder showed a capacity retention of 95% after over 1700 such cycles,” highlights Prof. Matsumi. The BP copolymer-based half-cells also showed a very high and stable coulombic efficiency, a measure that compares the amount of charge flowing in and out of the cell in a given cycle; this is also indicative of the long-term durability of the battery. Images of the binders taken with a scanning electron microscope before and after cycling revealed that only tiny cracks formed on the BP copolymer, whereas large cracks had already formed on PVDF in less than a third of the total number of cycles.

The theoretical and experimental findings of this study will pave the way for developing long-lasting Li-ion batteries. In turn, this could have far-reaching economic and environmental consequences, as Prof. Matsumi explains: “The realization of durable batteries will help in the development of more reliable products for long-term use. This will encourage consumers to purchase more expensive battery-based assets like electric vehicles, which will be used for many years.” He also remarks that durable batteries would be good news for those relying on artificial organs, such as patients with certain heart diseases. Of course, the general population would also benefit, considering how much smartphones, tablets, and laptops are used and recharged every day.

Further progress in electrode binders will hopefully put us closer to more durable battery-based products and a greener future.

Featured image: The BP copolymer offers several advantages that put it miles ahead of the conventional PVDF binder in terms of stability and durability © Noriyoshi Matsumi from JAIST


Reference: Agman Gupta, Rajashekar Badam, Aniruddha Nag, Tatsuo Kaneko, and Noriyoshi Matsumi, “Bis-imino-acenaphthenequinone-Paraphenylene-Type Condensation Copolymer Binder for Ultralong Cyclable Lithium-Ion Rechargeable Batteries”, ACS Appl. Energy Mater. 2021. https://doi.org/10.1021/acsaem.0c02742


Provided by Jaist

Novel Urine Test Developed to Diagnose Human Kidney Transplant Rejection (Medicine)

Study demonstrates potential for a noninvasive clinical test to diagnose kidney allograft rejection and ultimately improve transplant outcomes

Patients can spend up to six years waiting for a kidney transplant. Even when they do receive a transplant, up to 20 percent of patients will experience rejection. Transplant rejection occurs when a recipient’s immune cells recognize the newly received kidney as a foreign organ and refuse to accept the donor’s antigens. Current methods for testing for kidney rejection include invasive biopsy procedures, causing patients to stay in the hospital for multiple days. A study by investigators from Brigham and Women’s Hospital and Exosome Diagnostics proposes a new, noninvasive way to test for transplant rejection using exosomes — tiny vesicles containing mRNA — from urine samples. Their findings are published in the Journal of the American Society of Nephrology. 

“Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops,” said Jamil Azzi, MD, associate physician in the Division of Renal Transplant at the Brigham and an associate professor of Medicine at Harvard Medical School. “If rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges.”

Before this study, physicians ordered biopsies or blood tests when they suspected that a transplant recipient was rejecting the donor organ. Biopsy procedures pose risks of complications, and 70-80 percent of biopsies end up being normal. Additionally, creatinine blood tests do not always yield definitive results. Because of the limitations surrounding current tests, researchers sought alternate and easier ways to assess transplant efficacy. 

In this study, researchers took urine samples from 175 patients who were already undergoing kidney biopsies advised by physicians. From these samples, investigators isolated urinary exosomes from the immune cells of the newly transplanted kidneys. From these vesicles, researchers isolated protein and mRNA and identified a rejection signature — a group of 15 genes — that could distinguish between normal kidney function and rejection. Notably, researchers also identified five genes that could differentiate between two types of rejection: cellular rejection and antibody-mediated rejection.

“These findings demonstrate that exosomes isolated from urine samples may be a viable biomarker for kidney transplant rejection,” said Azzi.

This research differs from prior attempts to characterize urinary mRNA because clinicians isolated exosomes rather than ordinary urine cells. The exosomal vesicle protects mRNA from degrading, allowing for the genes within the mRNA to be examined for the match rejection signature. In previous research, mRNA was isolated from cells that shed from the kidney into urine. However, without the extracellular vesicles to protect the mRNA, the mRNA decayed very quickly, making this test difficult to do in a clinical setting.

“Our paper shows that if you take urine from a patient at different points in time and measure mRNA from inside microvesicles, you get the same signature over time, allowing you to assess whether or not the transplant is being rejected,” said Azzi. “Without these vesicles, you lose the genetic material after a few hours.”

One limitation to this research is that these tests were done on patients undergoing a biopsy ordered by their physician, who already suspected that something was wrong. In the future, Azzi and his colleagues aim to understand whether a test such as this one can be used on kidney transplant recipients with normal kidney activity as measured in the blood to detect hidden rejection (subclinical rejection). They are currently doing a second study on patients with stable kidney function, looking to see if the same signature they identified in this current study could be used on patients without previously identified issues but still detect subclinical rejection.

“What’s most exciting about this study is being able to tell patients who participated that their effort allowed us to develop something that can help more people in the future,” said Azzi. “As a physician-scientist, seeing an idea that started as a frustration in the clinic, and being able to use the lab bench to develop this idea into a clinical trial, that is very fulfilling to me.”

Funding for this work was provided by the American Heart Association (13FTF17000018), National Institutes of Health (RO1 AI134842), Exosome Diagnostics, NIH Clinical Center Grant (F32DK11106). Azzi reports having intellectual properties and receiving royalties from Accrue Health Inc.; receiving research funding from the American Diabetes Association, American Heart Association, and Qatar Research Fund; being a scientific advisor for CareDx; and having intellectual properties in Exosome Diagnostics. Co-authors are employees of Exosome Diagnostics, a Bio-Techne brand.


Reference: Azzi, J et al. “Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection” Journal of the American Society of Nephrology DOI:10.1681/ASN.2020060850


Provided by Brigham and Women Hospital

How Does Your Brain Process Emotions? Answer Could Help Address Loneliness Epidemic (Neuroscience)

Study finds specific brain regions respond opposingly to emotions related to loneliness and wisdom

Research over the last decade has shown that loneliness is an important determinant of health. It is associated with considerable physical and mental health risks and increased mortality. Previous studies have also shown that wisdom could serve as a protective factor against loneliness. This inverse relationship between loneliness and wisdom may be based in different brain processes.

In a study published in the March 5, 2021 online edition of Cerebral Cortex, researchers at University of California San Diego School of Medicine found that specific regions of the brain respond to emotional stimuli related to loneliness and wisdom in opposing ways.

“We were interested in how loneliness and wisdom relate to emotional biases, meaning how we respond to different positive and negative emotions,” said Jyoti Mishra, PhD, senior author of the study, director of the NEATLabs and assistant professor in the Department of Psychiatry at UC San Diego School of Medicine.

The study involved 147 participants, ages 18 to 85. The subjects performed a simple cognitive task of determining which direction an arrow was pointed while faces with different emotions were presented in the background.

Dilip Jeste, MD, is senior author of the study, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. © UC San Diego Health Sciences

“We found that when faces emoting anger were presented as distractors, they significantly slowed simple cognitive responses in lonelier individuals. This meant that lonelier individuals paid more attention to threatening stimuli, such as the angry faces.”

“For wisdom, on the other hand, we found a significant positive relationship for response speeds when faces with happy emotions were shown, specifically individuals who displayed wiser traits, such as empathy, had speedier responses in the presence of happy stimuli.”

Electroencephalogram (EEG)-based brain recordings showed that the part of the brain called the temporal-parietal junction (TPJ) was activating differently in lonelier versus wiser individuals. TPJ is important for processing theory of mind, or the degree of capacity for empathy and understanding of others. The study found it more active in the presence of angry emotions for lonelier people and more active in the presence of happy emotions for wiser people.

Researchers also noted greater activity to threatening stimuli for lonelier individuals in the left superior parietal cortex, the brain region important for allocating attention, while wisdom was significantly related to enhanced happy emotion-driven activity in the left insula of the brain, responsible for social characteristics like empathy.

“This study shows that the inverse relationship between loneliness and wisdom that we found in our previous clinical studies is at least partly embedded in neurobiology and is not merely a result of subjective biases,” said study author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine.

“These findings are relevant to the mental and physical health of individuals because they give us an objective neurobiological handle on how lonelier or wiser people process information,” said Mishra. “Having biological markers that we can measure in the brain can help us develop effective treatments. Perhaps we can help answer the question, ‘Can you make a person wiser or less lonely?’ The answer could help mitigate the risk of loneliness.”

The authors say next steps include a longitudinal study and an intervention study.

“Ultimately, we think these evidence-based cognitive brain markers are the key to developing better health care for the future that may address the loneliness epidemic,” said Mishra.

Co-authors include: Gillian Grennan, Pragathi Priyadharsini Balasubramani, Fahad Alim, Mariam Zafar-Khan, UC San Diego; and Ellen Lee, Veterans Affairs San Diego Healthcare System.

Featured image: Jyoti Mishra, PhD, is the senior author of the study, director of the NEATLabs and assistant professor in the Department of Psychiatry at UC San Diego School of Medicine. © UC San Diego Health Sciences


Reference: Gillian Grennan, Pragathi Priyadharsini Balasubramani, Fahad Alim, Mariam Zafar-Khan, Ellen E Lee, Dilip V Jeste, Jyoti Mishra, Cognitive and Neural Correlates of Loneliness and Wisdom during Emotional Bias, Cerebral Cortex, 2021;, bhab012, https://doi.org/10.1093/cercor/bhab012


Provided by University of California San Diego

Researchers Discover New Potential For Functional Recovery After Spinal Cord Injury (Medicine)

Researchers at Indiana University School of Medicine have successfully reprogrammed a glial cell type in the central nervous system into new neurons to promote recovery after spinal cord injury—revealing an untapped potential to leverage the cell for regenerative medicine.

The group of investigators published their findings March 5 in Cell Stem Cell. This is the first time scientists have reported modifying a NG2 glia—a type of supporting cell in the central nervous system—into functional neurons after spinal cord injury, said Wei Wu, PhD, research associate in neurological surgery at IU School of Medicine and co-first author of the paper.

Wu and Xiao-Ming Xu, PhD, the Mari Hulman George Professor of Neuroscience Research at IU School of Medicine, worked on the study with a team of scientists from the University of Texas Southwestern Medical Center. Xu is also a primary member of Stark Neurosciences Research Institute, where he leads the Indiana Spinal Cord and Brain Injury Research Group.

Spinal cord injuries affect hundreds of thousands of people in the United States, with thousands more diagnosed each year. Neurons in the spinal cord don’t regenerate after injury, which typically causes a person to experience permanent physical and neurological ailments.

“Unfortunately, effective treatments for significant recovery remain to be developed,” Xu said. “We hope that this new discovery will be translated to a clinically relevant repair strategy that benefits those who suffer from a spinal cord injury.”

When the spinal cord is injured, glial cells, of which there are three types—astrocyte, ependymal and NG2—respond to form glial scar tissue.

“Only NG2 glial cells were found to exhibit neurogenic potential in the spinal cord following injury in adult mice, but they failed to generate mature neurons,” Wu said. “Interestingly, by elevating the critical transcription factor SOX2, the glia-to-neuron conversion is successfully achieved and accompanied with a reduced glial scar formation and increased functional recovery following spinal cord injury.”

The researchers reprogrammed the NG2 cells from the mouse model using elevated levels of SOX2—a transcription factor found inside the cell that’s essential for neurogenesis—to neurons. This conversion has two purposes, Xu said: generate neurons to replace those lost due to a spinal cord injury and reduce the size of the glial scars in the lesion area of the damaged tissue.

This discovery, Wu said, serves as an important target in the future for potential therapeutic treatments of spinal cord injury.

The partnership between the laboratory of Chun-Li Zhang, PhD, professor at UT Southwestern Medical Center, and Xu’s laboratory at IU School of Medicine greatly benefited the research, Xu added, by offering complementary expertise in neuronal reprogramming and in spinal cord injury, respectively.

“Such a collaboration will be continued between the two laboratories to address neuronal remodeling and functional recovery after successful conversion of glial cells into functional neurons in future,” Xu said.


Reference: Wenjiao Tai, Wei Wu, Lei-Lei Wang et al., “In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury”, Cell stem cell, 2021. DOI: https://doi.org/10.1016/j.stem.2021.02.009


Provided by IU School of Medicine


About IU School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

Canadian Scientists And Swiss Surgeons Discover the Cause Of Excess Post-surgical Scarring (Medicine)

The finding could improve recovery from abdominal and pelvic surgery

The body is amazing at healing itself. However, sometimes it can overdo it. Excess scarring after abdominal and pelvic surgery within the peritoneal cavity can lead to serious complications and sometimes death. The peritoneal cavity has a protective lining containing organs within our abdomen. It also contains fluid to keep the organs lubricated. When the lining gets damaged, tissue and scarring can form, creating problems. Researchers at the University of Calgary and University of Bern, Switzerland, have discovered what’s causing the excess scarring and options to try to prevent it.

“This is a worldwide concern. Complications from these peritoneal adhesions cause pain and can lead to life-threatening small bowel obstruction, and infertility in women,” says Dr. Joel Zindel, MD, University of Bern, Switzerland, and first author on the study who worked on this research as a Swiss National Science Foundation research fellow at the University of Calgary. “People sometimes require a second surgery.”

The research published in Science, was conducted in mice and shows the excess scarring is caused by macrophages, a type of white blood cell that rushes to the surgical site to start to repair the injury.

“Joel developed a new method using the highly specialized imaging equipment in my lab that gave scientists the first look at what these macrophages are doing in real-time,” says Dr. Paul Kubes, PhD, principal investigator on the study and professor at the Cumming School of Medicine. “We are still working to understand why the macrophages take on this repair work as they are known for attacking pathogens. Whatever they are responding to, it’s clear their involvement is causing the scarring problem.”

The researchers also discovered two ways to inhibit this natural response. They either removed the macrophages, or they introduced a drug to block the macrophage stickiness. Both processes were very effective in stopping the adhesions.

“We believe the macrophage response has not made the evolutionary leap to understand that surgery is beneficial and not a threat to survival,” says Kubes. “It’s possible, that the body is reacting to the surgery, that having the organs exposed to the environment is interpreted as a threat, like an attack from a predator. The body doesn’t understand that the surgeon will do the critical repair work.”

Macrophages are also present in humans, and the research team believes the response seen in mice is likely to translate to both adults and children. They hope to move to trials on human cells, soon, and eventually clinical trials.

“Every surgeon does operations for people who have these abdominal adhesions,” says Zindel. “It would be amazing to be able to prevent this surgical complication. It would not only benefit individuals, it would create significant savings for the healthcare system, by reducing hospital costs for readmission and surgery.”

The basic research was funded by the Natural Sciences and Engineering Research Council while the clinical application was funded by the Canadian Institutes of Health Research (CIHR). Kubes is supported by Heart & Stroke and the CIHR Canada Research Chairs Program and Zindel is supported from a fellowship from the Swiss National Science Foundation.

This research was possible with support from the Nicole Perkins Microbial Communities Core Lab, the Live Cell Imaging Resource Laboratory at the Cumming School of Medicine, and the Microscopy Imaging Center (MIC) of the University of Bern.

Featured image: This is the view through a multi-photon microscope as macrophages (red) congregate at an injury site (green). © Supplied by Kubes’ Lab, Snyder Institute for Chronic Disease, Cumming School of Medicine, University of Calgary


Reference:  J. Zindel, M. Peiseler, M. Hossain, C. Deppermann, W. Y. Lee, B. Haenni, B. Zuber, J. F. Deniset, B. G. J. Surewaard, D. Candinas, P. Kubes, “Primordial GATA6 macrophages function as extravascular platelets in sterile injury”, Science  05 Mar 2021: Vol. 371, Issue 6533, eabe0595 DOI: 10.1126/science.abe0595


Provided by University of Calgary