Several drugs combined into one daily pill for seniors who have trouble remembering to take their medications.

Drugs printed at your local pharmacy at personalized dosages that best suit your health needs.

These are just a few potential advantages of 3D drug printing, a new system for manufacturing drugs and treatments on-site at pharmacies, health care facilities and other remote locations.

In 2015, the Food and Drug Administration approved the first 3D-printed drug, Spritam (levetiracetam), for epilepsy. Several other manufacturers and drug companies are developing their own ones.

But the widespread adoption of 3D drug printing will require stringent quality control measures to ensure that people get the right medication and dosage. Even a tiny mismeasurement of a drug’s ingredient during the printing process could endanger a patient’s health.

In a new research paper, NIST research scientist Thomas P. Forbes assesses various approaches to ensuring that 3D drug printers work as designed. The journal article applies a “quality by design” analysis to evaluate the best procedures and protocols to ensure that 3D printers produce drugs at the correct dosages and with the correct mix of chemicals.

Though various methods exist for remotely printing drugs, Forbes focused on one of the most common: inkjet printers and similar systems that can print personalized medication on demand.

Like inkjet printers in homes, though larger, the printer has nozzles that deposit the drug’s liquified materials, or inks, into tiny wells on a tray or directly into capsules. Through freeze-drying and other processes, the liquid can be turned into a tablet or powder poured into a capsule. It can also be evaporated onto a thin film that dissolves in the mouth.

Forbes’ paper does not make any recommendations. Instead, his research identifies and tests several possible methods and techniques for maintaining quality control in 3D drug printing.

Jeanie Tryggestad, M.D., an associate professor of pediatrics in the OU College of Medicine, led the study, which is published in The Journal of Clinical Endocrinology & Metabolism. It marks one of the first times microRNA abundance has been explored to predict the progression of Type 2 diabetes in youth. The specific microRNAs in the study are involved in insulin resistance and other actions that can stress beta cells or cause their death. The research is significant because it points to a process that is necessary to understand in order to ultimately design a strategy for prevention.

“Type 2 diabetes in youth is so aggressive, and the decline of beta cell function in youth is much more than we see in adults,” Tryggestad said. “We believe that predicting what will cause beta cell dysfunction, and eventually preventing that dysfunction, is one of the keys for preventing or treating Type 2 diabetes.”

Tryggestad’s study showed that the microRNAs, at baseline, were nearly as effective as A1C measurement (average level of blood sugar) when predicting who would fail to respond to treatment for Type 2 diabetes. Treatment failure was defined as having an A1C of greater than 8% for six months or a circumstance that caused the study participant to go back on insulin without the ability to come back off. Circulating microRNAs also predicted a 20% decrease in beta cell function during the first six months of the study.

Currently, microRNAs can be measured only in a research setting, not in a clinic, but that may change in the future, Tryggestad said. The study’s implications are important not only for the predictive potential of microRNAs, but because they represent a mechanism, or part of the process by which Type 2 diabetes develops and worsens.

“Glucose and A1C are relevant to me as a clinician, but as a clinician-researcher, it’s important to have this additional piece of information about microRNAs because it points us toward a mechanism. It’s the mechanism that we need to understand to design a prevention. It adds a layer of understanding that we haven’t had before,” she said.

Addressing the dramatic increase in Type 2 diabetes in children is only becoming more critical. Each year in the United States, cases of Type 2 diabetes in youth increase by 5.3%. At that rate, the prevalence is expected to increase by a staggering 700% by the year 2060. Tryggestad said that today, more youth ages 15 to 19 are living with Type 2 diabetes than Type 1 diabetes — the first time that has ever happened.

The samples analyzed in this research came from participants in the landmark TODAY study (Treatment Options for Type 2 Diabetes in Adolescents and Youth). The OU College of Medicine played a major role in the multi-center clinical trial, which began recruiting participants in 2003 and ended in 2020. The trial featured 699 study participants, and Oklahoma enrolled more patients than any other participating site.

The trial was the first and largest of its kind to compare treatments for Type 2 diabetes in youth, but it has continued to yield information since the original study ended. The OU College of Medicine was awarded an additional grant to analyze microRNA samples taken during the first 10 years of the study.

New research, published today in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) — chemicals which do not break down in nature — can permeate the skin barrier and reach the body’s bloodstream.

PFAS are used widely in industries and consumer products from school uniforms to personal care products because of their water and stain repellent properties. While some substances have been banned by government regulation, others are still widely used and their toxic effects have not yet been fully investigated.

PFAS are already known to enter the body through other routes, for example being breathed in or ingested via food or drinking water, and they are known to cause adverse health effects such as a lowered immune response to vaccination, impaired liver function and decreased birth weight.

It has commonly been thought that PFAS are unable to breach the skin barrier, although recent studies have shown links between the use of personal care products and PFAS concentrations in human blood and breast milk. The new study is the most comprehensive assessment yet undertaken of the absorption of PFAS into human skin and confirms that most of them can enter the body via this route.

Lead author of the study, Dr Oddný Ragnarsdóttir carried out the research while studying for her PhD at the University of Birmingham. She explained: “The ability of these chemicals to be absorbed through skin has previously been dismissed because the molecules are ionised. The electrical charge that gives them the ability to repel water and stains was thought to also make them incapable of crossing the skin membrane.

“Our research shows that this theory does not always hold true and that, in fact, uptake through the skin could be a significant source of exposure to these harmful chemicals.”

The researchers investigated 17 different PFAS. The compounds selected were among those most widely used, and most widely studied for their toxic effects and other ways through which humans might be exposed to them. Most significantly, they correspond to chemicals regulated by the EU’s Drinking Water Directive.

In their experiments the team used 3D human skin equivalent models — multilayered laboratory grown tissues that mimic the properties of normal human skin, meaning the study could be carried out without using any animals. They applied samples of each chemical to measure what proportions were absorbed, unabsorbed, or retained within the models.

Of the 17 PFAS tested, the team found 15 substances showed substantial dermal absorption — at least 5% of the exposure dose. At the exposure doses examined, absorption into the bloodstream of the most regulated PFAS (perfluoro octanoic acid (PFOA)) was 13.5% with a further 38% of the applied dose retained within the skin for potential longer-term uptake into the circulation.

The amount absorbed seemed to correlate with the length of the carbon chain within the molecule. Substances with longer carbon chains showed lower levels of absorption, while compounds with shorter chains that were introduced to replace longer carbon chain PFAS like PFOA, were more easily absorbed. Absorption of perfluoro pentanoic acid for example was four times that of PFOA at 59%.

Study co-author, Dr Mohamed Abdallah, said “our study provides first insight into significance of the dermal route as pathway of exposure to a wide range of forever chemicals. Given the large number of existing PFAS, it is important that future studies aim to assess the risk of broad ranges of these toxic chemicals, rather than focusing on one chemical at a time.”

Study co-author, Professor Stuart Harrad, of the University of Birmingham’s School of Geography, Earth and Environmental Sciences, added: “This study helps us to understand how important exposure to these chemicals via the skin might be and also which chemical structures might be most easily absorbed. This is important because we see a shift in industry towards chemicals with shorter chain lengths because these are believed to be less toxic — however the trade-off might be that we absorb more of them, so we need to know more about the risks involved.”

In a world-first study published last weekend in the journal Cognition, a team of international researchers has reported some surprising findings relating to facial recognition.

The first discovery is that one’s ability to recognise faces has nothing to do with how extraverted, sociable, or gregarious a person is. What is clear, however, is that good facial recall is linked to the number of close, high-quality relationships that people have.

Researchers from the University of South Australia (UniSA), University of Western Australia (UWA) and Curtin University, along with US colleagues from Wellesley College and Harvard Medical School, undertook four separate studies involving more than 3000 people to tease out the relationship between facial recognition, social networks and personality traits.

In tests where participants memorised new faces or identified celebrity faces, their scores correlated with the number of close relationships they enjoyed.

“People who identified more faces typically had larger supportive social networks, which bodes well for their overall health and happiness,” says lead researcher UniSA psychologist Dr Laura Engfors.

“In concrete terms, the rise from the lowest (two) to the highest (28) number of faces that were successfully recognised on one test coincided with six additional close relationships, increasing from nine to 15. That’s an increase of two thirds and it is one extra strong social bond per four famous people recognised.”

The research did not find any link between facial recognition and a more social personality.

“Our findings rule out the idea that being sociable means you’ll probably be great at recognising faces. It also helps to dispel the common misconception that not recognising someone means you are less sociable.

“The ability to recognise faces more easily also means people may develop relationships faster.

“Imagine you’ve had an engaging conversation with someone you have only just met. A few weeks later you run into them again. If you recognise them quickly and easily, it opens the door to develop the rapport you established in your first meeting, helping the relationship to progress.

“On the flip side, if you don’t recognise them, you’ve missed the chance to build on that initial interaction,” Dr Engfors says.

Curtin University researcher and co-author Dr Linda Jeffery says being recognised by someone is a boost to a person’s self-esteem.

“It can make us feel important and valued, leading us to relate to that person more warmly, whereas we feel snubbed if someone we have met before does not recognise us.”

Wellesley College psychologist and co-author Associate Professor Jeremy Wilmer hopes the findings will be used to build stronger communities that facilitate human connection.

“Understanding that not everyone finds it easy to recognise people can help us to support those around us in social interactions,” Prof Wilmer says.

“Something as simple as name tags at a community barbecue or school event can make the difference between a connection built and a connection lost. Similarly, if you catch a flicker of uncertainty on someone’s face when you say hello, a subtle reminder to help them place you will be appreciated.”

People can test their own celebrity face recognition at the researchers’ citizen science website TestMyBrain.org.

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.

“We wanted to get these proteins out of the cell membrane, so we redesigned them as hyperstable, soluble analogues, which look like membrane proteins but are much easier to work with,” explains Casper Goverde, a PhD student in the Laboratory of Protein Design and Immunoengineering (LPDI) in the School of Engineering.

In a nutshell, Goverde and a research team in the LPDI, led by Bruno Correia, used deep learning to design synthetic soluble versions of cell membrane proteins commonly used in pharmaceutical research. Whereas traditional screening methods rely on indirectly observing cellular reactions to drug and antibody candidates, or painstakingly extracting small quantities of membrane proteins from mammalian cells, the researchers’ computational approach allows them to remove cells from the equation. After designing a soluble protein analogue using their deep learning pipeline, they can use bacteria to produce the modified protein in bulk. These proteins can then bind directly in solution with molecular candidates of interest.

“We estimate that producing a batch of soluble protein analogues using E. coli is around 10 times less expensive than using mammalian cells,” adds PhD student Nicolas Goldbach.

The team’s research has recently been published in the journal Nature.

Flipping the script on protein design

In recent years, scientists have successfully harnessed artificial intelligence networks that use deep learning to design novel protein structures, for example by predicting them based on an input sequence of amino acid building blocks. But for this study, the researchers were interested in protein folds that already exist in nature; what they needed was a more accessible, soluble version of these proteins.

“We had the idea to invert this deep learning pipeline that predicts protein structure: if we input a structure, can it tell us the corresponding amino acid sequence?” explains Goverde.

To achieve this, the team used the structure prediction platform AlphaFold2 from Google DeepMind to produce amino acid sequences for soluble versions of several key cell membrane proteins, based on their 3D structure. Then, they used a second deep learning network, ProteinMPNN, to optimize those sequences for functional, soluble proteins. The researchers were pleased to discover that their approach showed remarkable success and accuracy in producing soluble proteins that maintained parts of their native functionality, even when applied to highly complex folds that have so far eluded other design methods.

“The holy grail of biochemistry”

A particular triumph of the study was the pipeline’s success in designing a soluble analogue of a protein shape known as the G-protein coupled receptor (GPCR), which represents around 40% of human cell membrane proteins and is a major pharmaceutical target.

“We showed for the first time that we can redesign the GPCR shape as a stable soluble analogue. This has been a long-standing problem in biochemistry, because if you can make it soluble, you can screen for novel drugs much faster and more easily,” says LPDI scientist Martin Pacesa.

The researchers also see these results as a proof-of-concept for their pipeline’s application to vaccine research, and even cancer therapeutics. For example, they designed a soluble analogue of a protein type called a claudin, which plays a role in making tumors resistant to the immune system and chemotherapy. In their experiments, the team’s soluble claudin analogue retained its biological properties, reinforcing the pipeline’s promise for generating interesting targets for pharmaceutical development.

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.

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.

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.

Their work — published today in leading journal Nature Communications — could have significant, wide-ranging impacts across a suite of industries, from food production to human health.

Enzymes are central to life and key to developing innovative drugs and tools to address society’s challenges. They have evolved over billions of years through changes in the amino acid sequence that underpins their 3D structure. Like beads on a string, each enzyme is composed of a sequence of several hundred amino acids that encodes its 3D shape.

With one of 20 amino acid ‘beads’ possible at each position, there is enormous sequence diversity possible in nature. Upon formation of their 3D shape, enzymes carry out a specific function such as digesting our dietary proteins, converting chemical energy into force in our muscles, and destroying bacteria or viruses that invade cells. If you change the sequence, you can disrupt the 3D shape, and that typically changes the functionality of the enzyme, sometimes rendering it completely ineffective.

Finding ways to improve the activity of enzymes would be hugely beneficial to many industrial applications and, using modern tools in molecular biology, it is simple and cost-efficient to engineer changes in the amino acid sequences to facilitate improvements in their performance. However, randomly introducing as little as three or four changes to the sequence can lead to a dramatic loss of their activity.

Here, the scientists report a promising new strategy to rationally engineer an enzyme called “beta-lactamase.” Instead of introducing random mutations in a scattergun approach, researchers at the Broad Institute and Harvard Medical School developed an algorithm that takes into account the evolutionary history of the enzyme.

“At the heart of this new algorithm is a scoring function that exploits thousands of sequences of beta-lactamase from many diverse organisms. Instead of a few random changes, up to 84 mutations over a sequence of 280 were generated to enhance functional performance,” said Dr Amir Khan, Associate Professor in Trinity College Dublin’s School of Biochemistry and Immunology, one of the co-authors of the research.

“And strikingly, the newly designed enzymes had both improved activity and stability at higher temperatures.”

Eve Napier, a second-year PhD student at Trinity College Dublin, determined the 3D experimental structure of a newly designed beta-lactamase, using a method called X-ray crystallography.

Her 3D map revealed that despite changes to 30% of the amino acids, the enzyme had an identical structure to the wild-type beta-lactamase. It also revealed how coordinated changes in amino acids, introduced simultaneously, can efficiently stabilise the 3D structure — in contrast to individual changes that typically impair the enzyme structure.

Eve Napier said: “Overall, these studies reveal that proteins can be engineered for improved activity by dramatic ‘jumps’ into new sequence space.

“The work has wide ranging applications in industry, in processes that require enzymes for food production, plastic-degrading enzymes, and those relevant to human health and disease, so we are quite excited for the future possibilities.”