All brain activity — from memory and emotion to learning and motor control — is made possible through communication across synapses, the connections between neurons. When this communication is unsuccessful, various conditions such as epilepsy can occur. A neuron is a type of cell that specializes in communicating with other cells by sending out chemical signals, called neurotransmitters, into synapses. In the brain, there are 100 trillion synapses between neurons.

The way neurons communicate has been studied for decades, but research published today in Science showcases models derived from hundreds of thousands of high-resolution images that reveal synaptic function with new clarity.

Led by Dr. John Rubinstein, Senior Scientist in the Molecular Medicine program, and Dr. Claire Coupland, first author and postdoctoral fellow in the Rubinstein Lab, the research team hopes that by capturing images of and modeling how chemicals are released from neurons, they may be able to inform new therapeutic targets that help improve care for children with epilepsy and other neurological conditions.

On the publication of these findings, Rubinstein shares how his team captured the images, and what their findings could mean for patients in the future.

What did your research uncover about the way neurons communicate?

When communicating, neurons release neurotransmitters into a synapse to be delivered to a receiving neuron. These neurotransmitters are released from small packets called synaptic vesicles. Once a message is received, the neurotransmitters must be reabsorbed and repackaged into new synaptic vesicles to clear out the synapse and make room for the next signal.

To facilitate this process, an enzyme called the vesicular-type ATPase (V-ATPase) acts as a pump to drive neurotransmitters into synaptic vesicles. V-ATPase also regulates neurotransmitter release from the vesicles.

In our research, we learned that the way V-ATPase controls the process of neurotransmitter release from synaptic vesicles is by spontaneously falling apart after the vesicles are loaded. We found that when we filled the synaptic vesicles with neurotransmitters, the V-ATPases split into two parts, which then allows neurotransmitter release.

How did you capture images of this process?

By using novel biochemical methods and novel imaging methods supported by the SickKids Nanoscale Biomedical Imaging Facility, we were able to isolate synaptic vesicles and obtain images of them. From there, we developed new computational approaches to analyze the images to show the V-ATPase in the vesicles at high resolution — something that has not been done before.

We created 3D models of the V-ATPase based on images we captured using cryogenic electron microscopy (cryo-EM), a method that images samples at -196 C. Our team saw that V-ATPase interacts with several components of the synaptic vesicle, which contains many proteins and lipids that are involved in neurotransmitter release.

Most surprisingly, we learned that the V-ATPase interacts with a protein called synaptophysin. By weight, synaptophysin is the most abundant synaptic vesicle protein. Until now, its function in neurons was not understood. What we found shows that synaptophysin could be helping to recruit V-ATPase to synaptic vesicles when they initially form.

What are the next steps for this research?

Now that we have discovered that V-ATPase interacts with synaptophysin in synaptic vesicles, we are working with Dr. Lu-Yang Wang, a Senior Scientist in the Neurosciences & Mental Health program, to understand the role of this interaction in the brain. We also want to understand how the loading of vesicles leads to the V-ATPase falling apart, and how this process controls the release of neurotransmitters from neurons.

In the future, this process could be a therapeutic target for many health conditions, including some kinds of epilepsy.

This research was funded by the Canadian Institutes of Health Research (CIHR), University of Toronto and the Natural Sciences and Engineering Research Council (NSERC). Infrastructure in the Nanoscale Biomedical Imaging Facility was supported by the Canada Foundation for Innovation and the Ontario Research Fund.

But it’s too soon to know if the so-called “blood oranges” are a viable crop for the Florida citrus industry, says Ali Sarkhosh, a UF/IFAS associate professor of horticultural sciences. Sarkhosh’s post-doctoral associate Fariborz Habibi explains further.

“Although blood oranges typically command higher prices than other common varieties, such as navel or Valencia oranges, it is unclear if farmers could substantially increase their per-acre income by adding them to their crop selection and then storing them for internal color development,” said Habibi, lead author of the study. “Improved fruit quality from the storage method presents a promising opportunity for the Florida citrus industry. However, further study is needed before recommending anything to growers.”

The fruit is rich in anthocyanins, which have been linked to various health benefits, including anti-inflammatory and antioxidant properties. They also contain other beneficial phytochemicals such as vitamin C, flavonoids and dietary fiber.

“Fruit can also develop internal color under similar conditions at home. However, the fruit in the supermarket should have a good internal color and be ready for consumption,” Sarkhosh said.

For this research, scientists harvested fruit from a research plot at the UF/IFAS North Florida Research and Education Center in Quincy.

Scientists found that storing the blood oranges at 40 to 53 degrees enhances anthocyanin, phenolic content, and antioxidants. When they lowered the temperatures 43 to 46 degrees, they also preserved fruit firmness, weight loss and sugar content.

“Attributes such as firmness are crucial for maintaining the overall quality, texture and taste of the blood oranges during storage,” said Habibi.

Blood oranges get their name from their deep red flesh. Their skin contains a type of antioxidant pigment. The fruit is commonly grown in countries like Italy and Spain, which have the Mediterranean climate – cold, but above 32 degrees — that helps them grow. In the United States, blood oranges grow primarily in California, but are not grown commercially yet in Florida.

Anthocyanin develops when the fruit is exposed to cold temperatures between 46 and 59 degrees for at least 20 days. Such conditions are rare in Florida’s subtropical climate.

Understanding the Study

Genomic disorders occur when there are changes or mutations in DNA that disrupt normal biological functions. These can lead to a range of health issues, including developmental delays and neurological problems. One type of complex DNA mutation involves a structure known as a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP). This study delves into how these complex rearrangements form and their impact on human health.

Key Findings

The research team, led by PNRI Assistant Investigator Cláudia Carvalho, Ph.D., collaborated with her lab colleagues, study lead author Christopher Grochowski, Ph.D., from the James R. Lupski Lab at Baylor College of Medicine, and other scientists to analyze the DNA of 24 individuals with inverted triplications.

They discovered that these rearrangements are caused by segments of DNA switching templates during the repair process. Normally, DNA repair mechanisms use the undamaged complementary strand as a template to accurately repair the damaged DNA. However, sometimes during repair, the repair machinery may inadvertently switch to a different but similar sequence elsewhere in the genome.

These switches occur within pairs of inverted repeats — sections of DNA that are mirror images of each other. Inverted repeats can confuse the repair machinery, leading to the use of the wrong template, which can disrupt normal gene function and contribute to genetic disorders.

1. Structural Diversity: The study found that these inverted triplications generate a surprising variety of structural variations in the genome, which can lead to different health outcomes.
2. Gene Dosage Impact: These rearrangements can alter the number of copies of certain genes, known as gene dosage. The correct number of gene copies is crucial for normal human development and function. Changes in gene dosage can cause diseases like MECP2 duplication syndrome, a rare neurodevelopmental disorder.
3. Mapping Breakpoints: By using advanced DNA sequencing techniques, the researchers identified the precise locations where these DNA segments switch templates leading to an altered number of genes including MECP2.

Dr. Carvalho and Baylor scientists first observed this pathogenic genomic structure in 2011 while studying MECP2duplication syndrome. Only recently, with the advent of long-read sequencing technology, has it become possible to investigate in detail how it forms in the genome.

Implications for Rare Disease Research and Treatment

“This study sheds light on the intricate mechanisms driving genetic rearrangements and their profound impact on rare diseases,” said Dr. Cláudia Carvalho, PNRI’s lead scientist on the study. “By unraveling these complex DNA structures, we open new avenues for understanding the genetic causes of rare diseases and developing targeted treatments to improve patient outcomes.”

These findings are being applied in a follow-up study led by Baylor’s Davut Pehlivan, M.D., investigating how complex genomic structures influence the clinical features of MECP2 duplication syndrome and their impact on targeted therapeutic approaches.

Carbon dioxide (CO₂) emissions are a major contributor to global warming, highlighting the pressing need for emission reduction measures. Consequently, there is a growing exploration of alternatives to fossil fuels, the primary source of CO₂ emissions. Methanol emerges as a versatile and cost-effective fuel, offering a promising alternative to conventional transportation fuels. Furthermore, in efforts to mitigate the impact of these emissions, there has been significant attention directed towards CO₂ capture and utilization technologies. These innovative approaches involve capturing CO₂ from the atmosphere and converting it into value-added products. Methanol synthesis via CO₂ hydrogenation stands out as a particularly promising method among these technologies.

For methanol synthesis via CO₂ hydrogenation, lower reaction temperatures are preferable since heat is released during the reaction. Accordingly, studies have focused on the development of catalysts that exhibit high activities at low temperatures. Copper-zinc oxide (Cu-ZnO) based catalysts are particularly favorable for this purpose due to their ability to form a Cu-ZnO interface that binds and converts CO₂ into formate intermediates which, in turn, promote methanol production. Increasing the surface area of this interface is an effective way to improve production, which can be achieved by increasing the dispersion of Cu nanoparticles. However, Cu nanoparticles are thermally unstable, which aggregate during catalyst preparation and reaction, thus reducing the interface area. Furthermore, the formation of water as a by-product of methanol synthesis accelerates Cu aggregation and inhibits formate formation.

To address these issues, a team of researchers, led by Professor Teruoki Tago from the Department of Chemical Science and Engineering, School of Materials and Chemical Technology at Tokyo Institute of Technology, developed novel Silicalite-1 (S-1) encapsulated Cu-ZnO catalysts. “Research indicates that encapsulating metals within porous carriers like silica or zeolite effectively mitigates thermal aggregation. Therefore, our focus shifted to developing a novel and efficient Cu-based catalyst for methanol production via CO₂ hydrogenation, placing particular emphasis on encapsulating Cu nanoparticles within porous materials.,” explained Tago. Their study was made available online on February 21, 2024, and published formally in Volume 485 of the Chemical Engineering Journal on April 1, 2024. The EU supported the project through their Horizon2020 Framework and the Japan Science and Technology Agency through SCICORP (Laurelin project).

The researchers fabricated two types of catalysts, one including a Cu/S-1 catalyst in which copper was loaded onto hydrophobic S-1 by impregnation, and the other Cu@S-1 catalyst, in which a Cu phyllosilicate (CuPS) powder was used as a metal source to encapsulate Cu particles in the S-1 zeolite. Cu@S-1 was prepared by reducing dissolved CuPS powder. The researchers investigated the dissolution time of the CuPS precursors on the catalyst properties, revealing that inappropriate dissolution times significantly affect the size of Cu particles. Optimal dissolution of the precursor resulted in a catalyst with approximately 2.4-nanometer Cu particles encapsulated within S-1, exhibiting optimal catalytic activity. This catalyst demonstrated higher hydrogenation activity and methanol production than Cu/S-1.

To further improve methanol production, ZnO was added to Cu@S-1 by impregnation, forming ZnO/Cu@S-1 catalyst with fine Cu particles. This catalyst demonstrated even higher activity, suggesting the formation of the Cu-ZnO interface. “Our findings indicate that the encapsulation structure with S-1 effectively suppresses thermal aggregation of Cu particles, while simultaneously facilitating the rapid elimination of the water byproduct from the vicinity of the Cu-ZnO interface, thus enhancing methanol synthesis,” remarked Tago.

Overall, this study demonstrates the effectiveness of the innovative encapsulation method for preparing highly active catalysts, offering a promising avenue for efficient methanol production from CO₂.

Professor Jonghun Kam from the Division of Environmental Science and Engineering at POSTECH used climate model simulations to examine individual effects of aerosols and greenhouse gases produced by human activities, focusing on the spring drought in 2022 that caused severe agricultural damage in the central Andes mountainous region. This research was recently published in the Bulletin of the American Meteorological Society, one of international journals in atmospheric science and meteorology.

Drought occurs when there is a prolonged absence of rainfall, leading to a lack of precipitation. It begins as a meteorological drought and progresses to an agricultural drought where the soil loses moisture. More severe droughts can escalate to hydrological droughts, characterized by reduced stream flows. When droughts significantly impact society and the economy, they are termed “socioeconomic droughts.”

The socioeconomic impact of drought is especially severe in societies and countries heavily dependent on agriculture. During the globally severe spring drought of 2022, the central Andean mountainous region of South America (including southern Peru, western Bolivia, and northern Chile), where agriculture is a major industry, experienced greater economic hardship than other regions. However, at that time, a shortage of human resources and funding limited an opportunity to better understand the causes of the 2022 drought.

In the study, Professor Jonghun Kam from POSTECH used 11 different climate models to analyze the impact of human activities on the spring drought that struck the Central Andean region in 2022, the most severe since 1951.

Climate model experiments revealed that human socio-economic activities have increased anthropogenic aerosols in the atmosphere, affecting its chemical composition and worsening the spring drought in the Central Andes. Conversely, the rise in greenhouse gases due to human activities has led to increased precipitation in the region, mitigating extreme spring droughts and reducing the likelihood of such events. Thus, aerosols and greenhouse gases from human activities have had opposite effects on atmospheric chemical composition and precipitation mechanisms.

The study is significant because it challenges previous conclusions that greenhouse gases are the primary cause of drought in South Africa and Iran, highlighting the need for more comprehensive research on the effects of human socio-economic activities.

Professor Jonghun Kam stated, “Some countries are disproportionately affected by extreme weather events due to the climate crisis, yet they often face the lacking of not only human but also financial resources to respond proactively.” He added, “Our goal is to address the global climate crisis by conducting research that supports these countries and thoroughly analyzing the impact of human activities on nature.”

The research was conducted with the support from the Basic Research Program of the National Research Foundation of Korea.

SQUID, short for Surrogate Quantitative Interpretability for Deepnets, is a computational tool created by Cold Spring Harbor Laboratory (CSHL) scientists. It’s designed to help interpret how AI models analyze the genome. Compared with other analysis tools, SQUID is more consistent, reduces background noise, and can lead to more accurate predictions about the effects of genetic mutations.

How does it work so much better? The key, CSHL Assistant Professor Peter Koo says, lies in SQUID’s specialized training.

“The tools that people use to try to understand these models have been largely coming from other fields like computer vision or natural language processing. While they can be useful, they’re not optimal for genomics. What we did with SQUID was leverage decades of quantitative genetics knowledge to help us understand what these deep neural networks are learning,” explains Koo.

SQUID works by first generating a library of over 100,000 variant DNA sequences. It then analyzes the library of mutations and their effects using a program called MAVE-NN (Multiplex Assays of Variant Effects Neural Network). This tool allows scientists to perform thousands of virtual experiments simultaneously. In effect, they can “fish out” the algorithms behind a given AI’s most accurate predictions. Their computational “catch” could set the stage for experiments that are more grounded in reality.

“In silico [virtual] experiments are no replacement for actual laboratory experiments. Nevertheless, they can be very informative. They can help scientists form hypotheses for how a particular region of the genome works or how a mutation might have a clinically relevant effect,” explains CSHL Associate Professor Justin Kinney, a co-author of the study.

There are tons of AI models in the sea. More enter the waters each day. Koo, Kinney, and colleagues hope that SQUID will help scientists grab hold of those that best meet their specialized needs.

Though mapped, the human genome remains an incredibly challenging terrain. SQUID could help biologists navigate the field more effectively, bringing them closer to their findings’ true medical implications.

For the study, rather than examine microbiome activity and composition linked to disease conditions — like anxiety and depression — the researchers wanted to flip the script and study the gut microbiome and brain in healthy, resilient people who effectively cope with different types of stress, including discrimination and social isolation.

“If we can identify what a healthy resilient brain and microbiome look like, then we can develop targeted interventions to those areas to reduce stress,” said Arpana Gupta, PhD, senior author and co-director of the UCLA Goodman-Luskin Microbiome Center. This is believed to be the first study to explore the intersection of resiliency, the brain, and the gut microbiome.

Gupta and her team focused on methods to cope with stress because research has shown that untreated stress can increase the risk of heart disease, stroke, obesity, and diabetes. While stress is an inevitable part of life, studying how to handle stress can help prevent developing diseases.

To conduct the study, published in Nature Mental Health, the researchers surveyed 116 people about their resiliency — like trust in one’s instincts and positive acceptance of change — and separated them into two groups. One group ranked high on the resiliency scale and the other group ranked low. The participants also underwent MRI imaging and gave stool samples two or three days before their scans.

The researchers found that people in the high resiliency group were less anxious and depressed, less prone to judge, and had activity in regions of the brain associated with emotional regulation and better cognition compared to the group with low resiliency. “When a stressor happens, often we go to this aroused fight or flight response, and this impairs the breaks in your brain,” Gupta said. “But the highly resilient individuals in the study were found to be better at regulating their emotions, less likely to catastrophize, and keep a level head,” added Desiree Delgadillo, postdoctoral researcher and one of the first authors.

The high resiliency group also had different microbiome activity than the low resiliency group. Namely, the high resiliency group’s microbiomes excreted metabolites and exhibited gene activity associated with low inflammation and a strong and healthy gut barrier. A weak gut barrier, otherwise known as a leaky gut, is caused by inflammation and impairs the gut barrier’s ability to absorb essential nutrients needed by the body while blocking toxins from entering the gut.

The researchers were surprised to find these microbiome signatures associated with the high resiliency group.

“Resilience truly is a whole-body phenomenon that not only affects your brain but also your microbiome and what metabolites that it is producing,” Gupta said. “We have this whole community of microbes in our gut that exudes these therapeutic properties and biochemicals, so I’m looking forward to building upon this research,” Delgadillo said.

The team’s future research will study whether an intervention to increase resilience will change brain and gut microbiome activity. “We could have treatments that target both the brain and the gut that can maybe one day prevent disease,” Gupta said.

A new UCLA Health study has found that resilient people exhibit neural activity in the brain regions associated with improved cognition and regulating of emotions, and were more mindful and better at describing their feelings. The same group also exhibited gut microbiome activity linked to a healthy gut, with reduced inflammation and gut barrier.

For the study, rather than examine microbiome activity and composition linked to disease conditions — like anxiety and depression — the researchers wanted to flip the script and study the gut microbiome and brain in healthy, resilient people who effectively cope with different types of stress, including discrimination and social isolation.

“If we can identify what a healthy resilient brain and microbiome look like, then we can develop targeted interventions to those areas to reduce stress,” said Arpana Gupta, PhD, senior author and co-director of the UCLA Goodman-Luskin Microbiome Center. This is believed to be the first study to explore the intersection of resiliency, the brain, and the gut microbiome.

Gupta and her team focused on methods to cope with stress because research has shown that untreated stress can increase the risk of heart disease, stroke, obesity, and diabetes. While stress is an inevitable part of life, studying how to handle stress can help prevent developing diseases.

To conduct the study, published in Nature Mental Health, the researchers surveyed 116 people about their resiliency — like trust in one’s instincts and positive acceptance of change — and separated them into two groups. One group ranked high on the resiliency scale and the other group ranked low. The participants also underwent MRI imaging and gave stool samples two or three days before their scans.

The researchers found that people in the h

Gupta and her team focused on methods to cope with stress because research has shown that untreated stress can increase the risk of heart disease, stroke, obesity, and diabetes. While stress is an inevitable part of life, studying how to handle stress can help prevent developing diseases.

To conduct the study, published in Nature Mental Health, the researchers surveyed 116 people about their resiliency — like trust in one’s instincts and positive acceptance of change — and separated them into two groups. One group ranked high on the resiliency scale and the other group ranked low. The participants also underwent MRI imaging and gave stool samples two or three days before their scans.

The researchers found that people in the high resiliency group were less anxious and depressed, less prone to judge, and had activity in regions of the brain associated with emotional regulation and better cognition compared to the group with low resiliency. “When a stressor happens, often we go to this aroused fight or flight response, and this impairs the breaks in your brain,” Gupta said. “But the highly resilient individuals in the study were found to be better at regulating their emotions, less likely to catastrophize, and keep a level head,” added Desiree Delgadillo, postdoctoral researcher and one of the first authors.

The high resiliency group also had different microbiome activity than the low resiliency group. Namely, the high resiliency group’s microbiomes excreted metabolites and exhibited gene activity associated with low inflammation and a strong and healthy gut barrier. A weak gut barrier, otherwise known as a leaky gut, is caused by inflammation and impairs the gut barrier’s ability to absorb essential nutrients needed by the body while blocking toxins from entering the gut.

The researchers were surprised to find these microbiome signatures associated with the high resiliency group.

“Resilience truly is a whole-body phenomenon that not only affects your brain but also your microbiome and what metabolites that it is producing,” Gupta said. “We have this whole community of microbes in our gut that exudes these therapeutic properties and biochemicals, so I’m looking forward to building upon this research,” Delgadillo said.

The team’s future research will study whether an intervention to increase resilience will change brain and gut microbiome activity. “We could have treatments that target both the brain and the gut that can maybe one day prevent disease,” Gupta said.

A new UCLA Health study has found that resilient people exhibit neural activity in the brain regions associated with improved cognition and regulating of emotions, and were more mindful and better at describing their feelings. The same group also exhibited gut microbiome activity linked to a healthy gut, with reduced inflammation and gut barrier.

For the study, rather than examine microbiome activity and composition linked to disease conditions — like anxiety and depression — the researchers wanted to flip the script and study the gut microbiome and brain in healthy, resilient people who effectively cope with different types of stress, including discrimination and social isolation.

“If we can identify what a healthy resilient brain and microbiome look like, then we can develop targeted interventions to those areas to reduce stress,” said Arpana Gupta, PhD, senior author and co-director of the UCLA Goodman-Luskin Microbiome Center. This is believed to be the first study to explore the intersection of resiliency, the brain, and the gut microbiome.

Gupta and her team focused on methods to cope with stress because research has shown that untreated stress can increase the risk of heart disease, stroke, obesity, and diabetes. While stress is an inevitable part of life, studying how to handle stress can help prevent developing diseases.

To conduct the study, published in Nature Mental Health, the researchers surveyed 116 people about their resiliency — like trust in one’s instincts and positive acceptance of change — and separated them into two groups. One group ranked high on the resiliency scale and the other group ranked low. The participants also underwent MRI imaging and gave stool samples two or three days before their scans.

The researchers found that people in the high resiliency group were less anxious and depressed, less prone to judge, and had activity in regions of the brain associated with emotional regulation and better cognition compared to the group with low resiliency. “When a stressor happens, often we go to this aroused fight or flight response, and this impairs the breaks in your brain,” Gupta said. “But the highly resilient individuals in the study were found to be better at regulating their emotions, less likely to catastrophize, and keep a level head,” added Desiree Delgadillo, postdoctoral researcher and one of the first authors.

The high resiliency group also had different microbiome activity than the low resiliency group. Namely, the high resiliency group’s microbiomes excreted metabolites and exhibited gene activity associated with low inflammation and a strong and healthy gut barrier. A weak gut barrier, otherwise known as a leaky gut, is caused by inflammation and impairs the gut barrier’s ability to absorb essential nutrients needed by the body while blocking toxins from entering the gut.

The researchers were surprised to find these microbiome signatures associated with the high resiliency group.

“Resilience truly is a whole-body phenomenon that not only affects your brain but also your microbiome and what metabolites that it is producing,” Gupta said. “We have this whole community of microbes in our gut that exudes these therapeutic properties and biochemicals, so I’m looking forward to building upon this research,” Delgadillo said.

The team’s future research will study whether an intervention to increase resilience will change brain and gut microbiome activity. “We could have treatments that target both the brain and the gut that can maybe one day prevent disease,” Gupta said.