The results, published in the June 21, 2024 online edition of New England Journal of Medicine, highlight the treatment’s potential to improve the quality of life for millions around the world affected by OSA.

“This study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author of the study, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.

OSA can result in reduced oxygen levels in the blood and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936 million.

Conducted in two Phase III, double-blinded, randomized, controlled trials, the new study cohort involved 469 participants diagnosed with clinical obesity and living with moderate-to-severe OSA. They were recruited from sites in nine different countries, including the U.S., Australia and Germany. Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing. Patients were administered either 10 or 15 mg of the drug by injection or a placebo. The impact of tirzepatide was evaluated over 52 weeks.

Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants that were given a placebo. Importantly, some participants that took the drug reached a point where CPAP therapy might not be necessary. Considerable data suggest that a drug therapy that targets both sleep apnea and obesity is beneficial rather than treating either condition alone.

Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.

“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnea, potentially leading to more personalized and effective treatment.”

Malhotra adds that having a drug therapy for OSA represents a significant advancement in the field.

“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless individuals and their families who have struggled with the limitations of existing treatments,” said Malhotra. “This breakthrough opens the door to a new era of OSA management for people diagnosed with obesity, potentially transforming how we approach and treat this pervasive condition on a global scale.”

Next steps include conducting clinical trials to examine longer term effects of tirzepatide.

Co-authors of the study include: Ronald Grunstein, University of Sydney; Ingo Fietze, University Hospital Berlin; Terri Weaver, University of Illinois Chicago; Susan Redline, Ali Azarbarzin, and Scott Sands, Harvard Medical School; Richard Schwab, University of Pennsylvania; and Julia Dunn, Sujatro Chakladar, Mathijs Bunck, and Josef Bednarik, Eli Lilly and Company.

Funding support for the study came, in part, from Eli Lilly and Company.

The test, developed by a team from the Broad Institute of MIT and Harvard and Princeton University, and supported by the US Centers for Disease Control and Prevention, uses CRISPR to distinguish between the two main types of seasonal flu, influenza A and B, as well as seasonal flu subtypes H1N1 and H3N2. It can also identify strains that resist antiviral treatment, and with further work, could potentially detect swine and avian flu strains, including H5N1, which is currently infecting cattle.

Appearing in The Journal of Molecular Diagnostics, the results could help improve outbreak response and clinical care by bringing tests that are accurate, low-cost, and fast to doctors’ offices and labs across the US and in other countries.

“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” said Cameron Myhrvold, co-senior author on the study along with Pardis Sabeti, an institute member at the Broad and a professor at Harvard University and the Harvard T.H. Chan School of Public Health, as well as a Howard Hughes Medical Institute investigator. Myhrvold, who is currently an assistant professor at Princeton University, was a postdoctoral researcher in Sabeti’s lab when the study began.

SHINE a light

The test is based on a technology called SHINE, which was developed by Sabeti’s lab in 2020 and uses CRISPR enzymes to identify specific sequences of viral RNA in samples. The researchers first used SHINE to test for SARS-CoV-2, and later to distinguish between the Delta and Omicron variants. Then, in 2022, they began adapting the assay to detect other viruses they knew were always circulating: influenzas. They wanted to create tests that could be used in the field or in clinics rather than hospitals or diagnostic labs with expensive equipment.

“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, co-first author on the study, a medical student at Harvard Medical School and an undergraduate researcher in Sabeti’s lab when the study began.

Typical diagnostic approaches such as polymerase chain reaction (PCR) require lengthy processing times, trained personnel, specialized equipment, and freezers to store reagents at -80°C, whereas SHINE can be conducted at room temperature in about 90 minutes. Currently, the assay only requires an inexpensive heat block to warm the reaction, and the researchers are working to streamline the process with the goal of returning results in 15 minutes.

The researchers also adapted SHINE to distinguish between different flu strains. In the future, they say the assay could be adapted to detect two different viruses with similar symptoms, such as influenza and SARS-CoV-2.

“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions,” said Jon Arizti-Sanz, a postdoctoral researcher in Sabeti’s lab and co-first author on the study.

For example, the tests could help clinicians decide whether to use Oseltamivir, a common antiviral that is effective for only some strains, Arizti-Sanz added. In the field, rapid testing could also help scientists collect samples more strategically during an outbreak to better monitor how the virus is spreading.

Next, the researchers are adapting SHINE to test for both avian and swine influenza strains. “With SARS-CoV-2 and now flu, we’ve shown that we can easily adapt SHINE to detect new or evolving viruses,” Arizti-Sanz said. “We’re excited to apply it to H5N1.”

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.