Monday, March 10, 2025

sleep duration blood sugar metabolic health

Sleep's Role in Metabolic Health: How It Impacts Blood Sugar Balance

Introduction

Credit: Vera Kratochvil/public domain

A study conducted by the Westlake Laboratory of Life Science and biomedicine in China reveals that insufficient sleep duration and delayed sleep onset contribute to heightened glycemic variability in adults. Continuous glucose monitoring (CGM) data showed that individuals with chronic sleep deprivation and late bedtimes exhibit greater fluctuations in blood glucose, potentially influencing strategies for diabetes prevention and control.

The Importance of Blood Sugar Regulation in Metabolic Health

Blood sugar regulations is essential for metabolic health, as glucose fluctuations are associated with diabetes-related complications. While prior studies have linked insufficient sleep to impaired glucose metabolism, the long-term effects of sleep patterns on glycemic variability remain insufficiently studied. To bridge this gap, researchers monitored sleep trajectories over several years to evaluate their influence on blood glucose regulation.

Study Overview: Linking Sleep Duration & Onset to Blood Sugar Variability

Research Methodology & Participants

A recent study, titled "Trajectories of Sleep Duration, Sleep Onset Timing, and Continuous Glucose Monitoring in Adults," published in JAMA Network Open, employed a prospective cohort approach to investigate the long-term effects of sleep duration and onset timing on glycemic variability.

The research examined 1,156 individuals, aged 46 to 83, from the Guangzhou Nutrition and Health Study, a long-term community-based cohort in Guangdong, China. Participants completed self-reported sleep assessments at multiple visits and used CGM devices for 14 consecutive days to track real-time blood glucose fluctuations.

Sleep Duration & Onset Timing Patterns

The study identified four distinct sleep duration trajectories:

  • Severe Inadequate Sleep (4.7 to 4.1 hours per night)
  • Moderate Inadequate Sleep (6.0 to 5.5 hours)
  • Mild Inadequate Sleep (7.2 to 6.8 hours)
  • Adequate Sleep (8.4 to 8.0 hours)

Additionally, two sleep onset timing patterns emerged:

  • Persistent early sleep onset
  • Persistent late sleep onset

How Sleep Affects Blood Sugar Stability

Impact of Sleep Duration on Glycemic Variability

According to CGM data, participants in the severe inadequate sleep category demonstrated:

  • A 2.87% elevation in glycemic variability (CV)
  • A 0.06 mmol/L increase in mean amplitude of daily glucose fluctuations (MODD)

Impact of Late Sleep Onset on Blood Sugar Levels

Analysis indicated that individuals with late sleep onset had:

  • 1.18% higher glycemic variability
  • 0.02 mmol/L increase in MODD

The Cumulative Effect of Poor Sleep Patterns

Notably, participants who exhibited both delayed sleep timing and reduced sleep duration displayed the most pronounced glucose fluctuations, reinforcing the notion of a cumulative metabolic burden.

The Need for Healthy Sleep Patterns

Prolonged insufficient sleep duration and delayed sleep onset were associated with heightened blood glucose variability, indicating their collective role in metabolic disturbances.

Key Takeway

Results highlight the importance of maintaining healthy sleep patterns, particularly adequate duration and early onset, in promoting glycemic stability and mitigating diabetes risks.

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Friday, March 7, 2025

AI deep tissue molecular imaging insect vision

The Future of Molecular Imaging: Insect Vision-Inspired Deep Tissue Mapping

Introduction: A Breakthrough in Molecular Imaging

Chemical tomographic image processing, inspired by the 'ommatidium' mechanism in 'bee vision,' is used to predict the heterogeneity of organoids. a) Hybrid compound mosaic images (2D tomography) are created by merging sensor chemistries within distinct layers. These images are processed using deep neural networks to predict organoid pixel information. b) Generative deep learning models, based on encoder-decoder U-net architectures, are employed for organoid image synthesis (details in Figure S14 of the Supporting Information). c) The application of 20 sensor chemistries from a spatiotemporally-resolved spectrometer results in synthetic superpositions for layers 2 and 3, creating distinctive mosaic arrangements (i-iii for M1-M3) while distinguishing them from media backgrounds (iv-v). Credit: Advanced Materials (2025), DOI: 10.1002/adma.202413017.

A recent study published in Advanced Materials unveils a novel technique for tracking molecular processes deep within tissue. Developed at the TechnionIsrael Institute of Technology, this breakthrough holds promise for advancing personlized medicine, cancer diagnostics, and early disease detection.

Study Leaders and Collaborators

The study was conducted under the leadership of Prof. Hossam Haick, alongside postdoctoral fellow Dr. Arnab Maity and Ph.D., candidate Vivian Darsa Maidantchik from the Technion's Wolfson Faculty of Chemical engineering. Collaborators included Dr. Dalit Barkan, research assistant Dr. Keren Weidenfeld, and Prof. Sarit Larisch from the Faculty of Natural Sciences at the University of Haifa.

Technion's Method: Functional and Molecular Mapping of Organoids

Technion researchers have developed a method for functional and molecular mapping of organoids3D cellular models that mimic the structural and functional properties of natural tissues. These organoids are instrumental in biomedical research, enabling scientists to:

  • Investigate disease mechanisms
  • Evaluate therapeutic interventions

Challenges in Organoid Tracking

Despite their promise, organoids encounter significant technological challenges, particularly in tracking internal tissue processes. Current techniques are costly and have notable drawbacks:

  • RNA sequencing: Destroy the tissue
  • Confocal Microscopy: Cannot probe deep-tissue activity

Technion's Cost-Effective & Non-Invasive Innovation

The Technion's innovation addresses these challenges with a cost-effective, precise, and non-invasive technique, enabling real-time monitoring of structural and molecular changes in organoids.

Visual of VOC spatiotemporal mapping and separation from organoids using a spatiotemporally-resolved spectrometer. b) VOC frequency spectrogram for analyzed organoids. c) 2D chemical tomography through sensor fusion. d) Schematic connecting VOCs with multi-dimensional imaging and cyto-proteo-genomics via generative AI. e) Scheme showing breast cancer progression through three stages: normal (MCF10A, M1), premalignant (MCF10AT, M2), and malignant (MCF10CA1h, M3), followed by f–h) DAPI staining, i–k) microscope imaging (x40, Bar = 50 µm), l) 3D representation, and m) western blot for mesenchymal markers (fibronectin, vimentin) and epithelial marker (E-Cadherin). n, o) Quantitative analysis of fibronectin and vimentin with statistical values. Credit: Advanced Materials (2025), DOI: 10.1002/adma.202413017.

Chemical Tomography: A New Method in Deep-Tissue Monitoring

The newly developed technique, known as chemical tomography, enables the functional analysis of tissues by detecting volatile organic compounds (VOCs) found in breath, saliva, sweat, and other bodily fluids.

VOC-Based Diagnostics in Disease Detection

Prof. Haick, a globally recognized authority in VOC-based diagnostics, has pioneered several breakthrough technologies for early disease detection.

Mapping the Molecular and Functional Landscape of Organoids

This study leveraged VOC monitoring to dynamically map the molecular and functional landscape of a human breast tissue organoid, uncovering critical protein and genomic markers linked to cancerous transformation.

AI-Driven Graphene Sensor System Inspired by Insect Vision

The system utilizes a graphene-based sensor array to detect VOCs, with the data being analyzed by generative artificial intelligence (AI).

Insect Vision as a Model for AI Processing

Drawing inspiration from insect compound eyes, where multiple small eyes provide various images to the brain:

  • Graphene sensors act as the 'eyes'
  • AI functions as the 'brain' for data processing and interpretation

Advantages of the New System

The innovative system enables real-time, dynamic mapping of organoids at a substantially reduced cost compared to conventional methods, while preserving tissue integrity. This breakthrough allows researchers to:

  • Monitor cancer progression across different stages
  • Enhance their understanding of cancer biology
  • Identify biochemical pathways, metabolic markers, and molecular processes involved in tumor development

Biochemical Pathways & Disease Biomarkers

Leveraging this novel approach, the researchers identified six key biochemical pathways responsible for generating 12 distinct VOCs, which have the potential to serve as biomarkers for various disease states.

Beyond Cancer: Future Applications in Personalized Medicine

Prof. Haick emphasized that beyond oncology, this system holds promise for diagnosing conditions affecting the kidneys, brain, and liver.

Real-Time Health Monitoring & AI Integration

Additionally, it can wirelessly transmit real-time physiological data to an external monitoring platform, facilitating continuous health tracking and early disease detectionmarking a significant advancement in AI-driven personalized medicine.

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Revolutionizing Deep Tissue Imaging with AI!

This breakthrough in molecular imaging is transforming personalized medicine and cancer diagnostics. With a graphene-based sensor array and AI-driven data analysis, researchers can now achieve real-time, non-invasive tissue mapping.

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Tuesday, March 4, 2025

epigenetic echoes violence genetic impact

Epigenetic Echoes: How Violence Imprints Lasting Genetic Marks on Future Generations

The 1982 Hama Massacre and Its Lasting Impact

The study is structured to compare genomic epigenetic markers in relation to varying degrees of violence exposure. Credit: Connie Mulligan.

In 1982, the Syrian government laid siege to Hama, resulting in the deaths of tens of thousands during sectarian violence. Four decades later, the memory of this massacre fueled rebels' efforts to overthrow the Assad regime responsible for the brutal act.

Genetic Imprints of War: A Legacy Passed Down

Another enduring consequence of the attack lies within the genetic makeup of Syrian families. Grandchildren of women who were pregnant during the siegedespite never experiencing the violence firsthandcarry its imprint in their genomes.

Epigenetics and the Transmission of Trauma

Inherited through maternal lineage, this genetic signature provides the first human evidence of a phenomenon previously observed only in animals—the intergenerational transmission of stress at the molecular level.

"Recognizing that trauma and violence can impact future generations should foster greater empathy and encourage policymakers to prioritize addressing violence," said Connie Mulligan, Ph.D., Professor of Anthropology and the Genetics Institute at the University of Florida, and senior author of the study.

"This phenomenon may offer insight into the persistent intergenerational cycles of abuse, poverty, and trauma observed worldwide, including in the United States."

How Trauma Leaves a Molecular Mark

While our DNA remains uncharged by lived experiences, epigenetic processes enable its functional tuning. Stress and environmental stimuli can lead to chemical modifications that adjust gene activity, potentially aiding adaptation, though the extent of these effects remains unclear.

Investigating the Epigenetic Legacy in Syrian Families

The chemical indicators identified by Mulligan and her team were the key targets in their investigation of Syrian family genetics. Although lab-based research has shown that animals can inherit stress-induced epigenetic modifications, demonstrating this humans has remained elusive.

A Groundbreaking Study on Generational Trauma

Mulligan collaborated with:

  • Rana Dajani, Ph.D., a molecular biologist at Hashemite University in Jordan
  • Catherine Panter-Brick, Ph.D., an anthropologist at Yale University, to carry out this groundbreaking study.

The research focused on tracking three generations of Syrian immigrants in the country.

The study's results were published in the journal Scientific Reports.

Three Generations, Three Unique Experiences

Some families experienced the Hama attack before seeking refuge in Jordan, while others avoided Hama but endured the recent civil war against the Assad regime.

The researchers gathered samples from grandmothers and mothers who were pregnant during the two conflicts, along with their children. This approach allowed for the inclusion of individuals who had encountered violence at distinct developmental stages.

A Control Group for Comparison

A third group consisted of families who had settled in Jordan before 1980, thereby avoiding the prolonged violence in Syria. These early immigrants provided a vital control group for comparison with families affected by the civil war.

The Science Behind the Study

Dajani, herself the daughter of refugees, worked intimately with the refugee community in Jordan to build rapport and encourage study involvement. She eventually obtained cheek swabs from 138 participants across 48 families.

"These families are eager to share their stories and have their voices heard," Mulligan remarked. "I believe we collaborated with every eligible family for this study."

Analyzing DNA for Epigenetic Modifications

In Florida, Mulligan's lab analyzed DNA for epigenetic modifications, investigating potential correlations with the families' exposure to violence.

The Lasting Epigenetic Impact of Violence

Genetic Markers Found in Grandchildren of Hama Survivors

Among the grandchildren of Hama survivors, researchers identified 14 genomic regions that had undergone modifications in response to the vilence experienced by their grandmothers. These findings suggest that stress-induced epigenetic changes can be inherited across generations, similar to patterns observed in animals.

Epigenetics Signatures in Directly Affected Individuals

The research identified 21 epigenetic sites in individuals who had directly experienced violence in Syria. Additionally, the study found that those exposed to violence in utero exhibited signs of accelerated epigenetic aging, a biological process potentially linked to increased susceptibility to age-related diseases.

A Shared Epigenetic Response to Stress

The majority of these epigenetic modifications exhibited a consistent pattern following exposure to violence, indicating a shared epigenetic response to stress —one that may impact not only those directly affected but also their descendants.

Broader Implications: Beyond War and Refugees

"Our research is applicable beyond refugee experiences; it extends to various forms of violence, including domestic abuse, sexual assault, and gun violence in the U.S.," Mulligan emphasized. "This issue warrants further study and greater attention."

Epigenetics and Human Health Risks

The precise impact of these epigenetic modifications on individuals carrying them remains uncertain. However, some studies have suggested a correlation between stress-induced epigenetic alterations and conditions such as diabetes.

A well-known study on Dutch famine survivors from World War II suggested that their descendants exhibited epigenetic modification associated with a higher likelihood ob obesity. While many such changes may be inconsequential, some could potentially impact human health, Mulligan noted.

Resilience Amid Trauma: A Testament to Human Strength

As Mulligan and her colleagues meticulously investigated the enduring genetic imprint of war and trauma, they were equally moved by the resilience of the families they studied. According to Mulligan, their narrative extended far beyond mere survival.

A Story Beyond Survival

"Despite enduring immense violence, these families extraordinary resilience. They continue to build meaningful lies, raise children, and uphold traditions," Mulligan remarked. "Such perseverance may be a distinctly human trait."

Source

"How does violence leave a lasting mark on our DNA? Discover groundbreaking research on inherited trauma and epigenetic changes."

Read the full article to explore how stress and trauma impact genetic memory and many affect future generations.

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Monday, February 17, 2025

impact hypnosis brain activity perception

New Research Shows How Hypnosis Modifies Brain Activity and Perception

Introduction to Hypnosis Research

fMRI imaging reveals areas of the brain where functional connectivity changes occur during the HS2 hypnosis state, shown in color (clockwise: rear, top, left, right). Credit: fMRI study, Mike Brügger, UZH.

Three studies form the University  of Zurich indicate that hypnosis modulates the functional connectivity of the brain's large networks and impacts the neurochemical environment in specific area.

The Scientific Enigma of Hypnosis

From a scientific standpoint, hypnosis has long remained an enigma. Until now, there has been insufficient data to determine whether it constitutes a a distinct state of human consciousness or is merely a product of imagination. Nevertheless, it continues to captivate researchers and the public alike.

Public and Scientific Interest in Hypnosis

Hypnosis continues to capture public and scientific interest, as evidenced by a recent in-depth feature in a leading women's magazine. Remarkable cases occasionally surface, including a 2018 incident at the Hirslanden Klinik St. Anna in Lucerne, where a 45-year-old patient underwent surgery to remove a metal plate from his lower arm under hypnosis alone. Without anesthesia or pain medication, the patient reported no significant pain, surprising the surgical team. This case was highlighted by the Swiss public broadcaster SRF Puls on September 17 of that year.

Clinical Application of Hypnosis

The integration of hypnosis into routine hospital care has shown promising results. Geneva University Hospitals (HUG) incorporate clinical hypnosis as a complementary approach alongside conventional treatments. To Support this initiative, HUG provides specialized training for its staff, as noted on its website. Additionally, hypnosis has been effectively employed to help alleviate anxiety in children facing upcoming medical procedures.

Impact of Hypnosis on Pain and Anxiety

Hypnosis appears to reduce pain and anxiety, making it a valuable tool in prenatal care, burn treatment and dental procedures.

Investigating the Altered Cognitive State in Hypnosis

The Neuroscientific Approach to Hypnosis

Until now, the precise effects of hypnosis on the human neurobiological system have remained elusive. Can hypnosis induce observable changes in brain activity, and if so, what do they entail? These critical questions motivated neuroscientists Philipp Stämpfli, Nuno Prates de Matos, and Mike Brügger, along with their research team, to investigate the phenomenon through three studies. Two of these studies were conducted at the Center for Magnetic Resonance Imaging at the University Hospital of Psychiatry Zurich (PUK), under Stämpfli's leadership, while the third was carried out in the Department of Psychology at the University of Zurich (UZH).

Exploring and characterizing various states of human consciousness remains one of the most significant challenges in neurobiology. Itis likely that alterations in states of consciousness manifest within the brain's functional networks. As a result, researchers hypothesized that any effects of hypnosis would be observable in these networks and could be mapped and quantified using advanced imaging techniques.

The Three Studies: Consistent Methodology

Study Design and Imaging Techniques

The neuroscientists carried out three studies with identical designs, employing distinct imaging techniques for each. This enabled them to investigate the effects of hypnosis on the human brain through a multimodal approach. The researchers assert that this was the first study to examine two distinct depths of hypnosis.

The fMRI research was published in Frontiers in Human Neuroscience, the EEG study in Cortex, and the magnetic resonance spectroscopy analysis in Scientific Reports.

Study Participants and Procedures

Each study involved the selection of just over 50 participants, all of whom were healthy, experienced in hypnosis and familiar with both hypnotic states. Once in the MR scanner, the participants were initially brought into a mild state of hypnosis (HS1, somnambulism) using a consistent, standardized induction. They were then guided into a deep, profound hypnotic state (HS2, Esdaile).

As all participants had prior experience with hypnosis, they were able to signal the study leaders from the scanner once they reached the desired depth. They maintained this state for approximately 20 minutes, which was the time required for brain imaging using one of the the three different methods.

The researchers acknowledge that the sample used in the three studies was highly selective. Therefore, they stress that the results should not be generalized. As Mike Brügger explains, "Our aim was to identify fundamental principles, specifically whether there are differences in brain activity when subjects are hypnotized to two distinct depths."

The primary objective of the three hypnosis studies was to gain a fundamental understanding of the processes occurring during hypnosis, rather than to explore its potential as a therapeutic approach.

The three studies provide evidence from various methodological approaches and verifiable data, demonstrating that scientists can differentiate between two levels of hypnosis.

Key Findings: Changes in Brain Activity and Connectivity

Evidence of Hypnosis Impacting Brain Activity

The fMRI study uncovered alterations in activity within the regions of the cerebral cortex associated with attention and body awareness. All participants reported experiencing a profound state of relaxation, which in some cases led to a loss of spatial temporal perception.

Elevated Theta Brainwaves

Theta brainwaves were elevated at both levels of hypnosis. These wave are associated with sleepiness and deep relaxation and also occur during other relaxation states such as meditation or psychedelic experiences. While they are present at various stages of the sleep cycle, they are not predominant during sleep.

In fact, while the subjects reported feeling deeply relaxed, they indicated that they were far from falling asleep. Instead, the researchers observed a high level of focus among the participants.

Physiological Changes Under Hypnosis

Under hypnosis, subjects exhibited a reduction in both breathing and heart rate, further confirming the deep relaxation associated with this state.

Analysis and Future Outlook

Challenges in Data Interpretation

While the three studies have accumulated a vast amount of scientific data, interpreting this data remains a challenging task, as acknowledged by the researchers. Nevertheless, St ämpfli and Brügger assert that the studies have already addressed two key questions.

The Impact of Hypnosis on Brain Activity

The first finding is that hypnosis does indeed alter brain activity, confirming that the hypnotic effect is neither imagined nor fabricated. The second insight is that hypnosis occurs at varying depths, a point that has been hotly debated within professional circles, with limited scientific evidence ot support it until now, according to Stämpfli.

Need for Further Research

While these recent findings mark progress, the researchers emphasize that additional studies are essential to develop a broader understanding of hypnosis. Furthermore, the underlying reasons for hypnosis' therapeutic effects on conditions like pain and anxiety warrant further investigation.

The Three Imaging Approaches

Three separate measurement methods were utilized by the researchers in the three hypnosis studies.

Electroencephalography (EEG)

Electroencephalography (EEG) was employed to monitor shifts in brainwave frequencies and spatial patterns within the electrical activity of millions of neurons.

Functional Magnetic Resonance Imaging (fMRI)

Functional Magnetic Resonance Imaging (fMRI) was used to capture alterations in inter-brain region communication and visually represent these changes.

Magnetic Resonance Spectroscopy (MRS)

Leveraging fMRI results, the researchers utilized magnetic resonance spectroscopy (MRS) to explore specific brain regions at a more detailed, molecular level.

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Explore the Science of Hypnosis and Brain Activity!

New research from the University of Zurich reveals how hypnosis alters brain function and perception. Dive into the latest findings on consciousness and neural connectivity.

Don't miss out  discover how hypnosis is reshaping neuroscience today!

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Thursday, February 13, 2025

worm surface chemistry growth survival

Worm Surface Chemistry Unlocks Clues to Their Growth and Survival

Groundbreaking Research Sheds Light on Worm's Surface Chemistry

Pristionchus pacificus showcases precise predation behavior. Wildtype adults of P. pacificus prey on C. elegans wildtype larvae, which possess distinct surface chemistry identified through 3D-OrbiSIMS analysis. Credit: University of Nottingham - Veeren Chauhan

Recent research has provided the most comprehensive analysis to date of the surface chemistry of worm species, shedding light on how these organisms engage with their surroundings and each other. This work could lay the groundwork for deeper insights into evolutionary changes, improve behavioral research and contribute to strategies for addressing parasitic infections.

The Role of Mass Spectrometry Imaging in Understanding Nematodes

Scientists from the University's School of Pharmacy utilized cutting-edge mass spectrometry imaging to study Caenorhabditis elegans and Pristionchus pacificus, aiming to elucidate their distinct surface chemical compositions and their roles in physiological and behavioral processes.

Nematode Surface Chemistry Reveals Complex Chemical Landscape

The study reveals that nematode surfaces primarily consist of oily, lipid-based compounds, creating a chemically intricate landscape. These findings have been published in the Journal of the American Chemical Society.

The Significance of Nematodes in Various Ecosystems

nematodes, commonly known as worms, inhabit diverse ecosystems worldwide, including soil, water, plants seeds, animals and even humans. In severe cases, nematode infections can result in significant health complications.

Insights into Human Biology Through Nematodes

Dr. Veeren Chauhan, Assistant Professor in Whole Organism Analytics the School of Pharmacy, led the research. He stated, "Nematodes serve as an exceptional model for human biology and are among the most comprehensively studied organisms, particularly in genetics, neurology and developmental biology."

Connecting Nematode Biology to Human Health

With humans sharing approximately 60-70% of their DNA these worms, new insights into their biology could profoundly advance our understanding of human physiology and aid in addressing global health challenges.

Cutting-Edge Technology Unlocks Nematode Chemical Properties

Leveraging state-of-the-art mass spectrometry technology, we investigated the surface chemical properties of nematodes across developmental stages, enabling us to monitor molecular changes, interspecies variations and their role in interactions.

Advancements in Mass Spectrometry: The 3D-OrbiSIMS Instrument

Utilizing the cutting-edge 3D-OrbiSIMS instrument at the University of Nottingham, the team uncovered dynamic changes in the surgace chemistry of both worm species, revealing a composition predominantly consisting of lipids (70-80%).

The Power of the 3D-OrbiSIMS Instrument for Chemical Analysis

The University of Nottingham was among the first institutions globally to acquire a 3D-OrbiSIMS instrument, facilitating cutting-edge molecular analysis of biological cells, tissues and various materials with unparalleled precision.

The Importance of Lipid Surfaces in Worm Physiology and Behavior

By integrating surface sensitivity, high mass resolution and spatial resolution with a depth-profiling sputtering beam, this instrument becomes an exceptionally powerful fool for chemical analysis, as evidenced in this study.

Lipid Layers Help Worms Survive and Interact

Dr. Chauhan explains, "identifying the lipid-dominated composition of these worm's surfaces represents a major breakthrough in comprehending their physiology. These lipid layers are essential for hydration retention and serve as a defense mechanism against bacterial invasion, which is critical for their survival."

Lipid Surfaces as Chemical Cues for Interspecies Interactions

Intriguingly, these lipids not only contribute to surface properties but also function as chemical signals that shape interspecies interactions, including predation. For instance, Pristionchus pacificus relies on direct contact with the surface lipids of Caenorhabditis elegans to initiate predatory behavior, with modifications in these lipids increasing the prey's vulnerability.

Implications for Parasitic Worm Research and Disease Prevention

This in-depth understanding of nematode surface chemistry and its role in interaction and survival paves the way for groundbreaking research, potentially informing novel strategies to combat parasitic worms and the diseases they propagate.

Collaboration with the Max Planck Institute for Neurobiology of Behavior

This study was carried out in collaboration with the Lightfoot Lab, under the leadership of Dr. James lightfoot, at the Max Planck Institute for Neurobiology of Behaviorcaesar in Bonn, Germany.

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Unlock the Secrets of Worm Surface Chemistry!

Recent breakthrough in worm surface chemistry reveal how lipid-based structures play a vital role in survival, interactions and even predation. This cutting-edge research could pave the way for new strategies to combat parasitic infections and enhance biological understanding.

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Friday, February 7, 2025

genome recoding for synthetic proteins

Scientists Recode the Genome to Create Programmable Synthetic Proteins

Breathrough in Genome Recoding

A codon, consisting of a three-nucleotide sequence in DNA or RNA, serves as a genetic instruction set for protein synthesis. It directs the cell to incorporate one of the 20 natural amino acids into a growing protein chain or, in the case of three specific 'stop' codons (TAG, TGA, and TAA), signals the termination of synthesis. Credit: Michael S. Helfenbein.

Yale synthetic biologists have successfully reprogrammed an organism's genetic code, creating a novel genomically recoded organism (GRO) with a single stop codon. Using a specially developed cellular platform, they have enabled the production of entirely new classes of synthetic proteins, which hold vast potential for advancing medical and industrial applications.

A Revolutionary Genomically Recoded Organism: 'Ochre'

What is 'Ochre'?

A groundbreaking genomically recoded organism (GRO), named 'Ochre,' has been developed by compressing redundant or 'degenerate' codons into a single codon. This achievement is detailed in a newly published study in Nature. Codons, sequences of three nucleotides in DNA or RNA, encode specific amino acids, the fundamental components of proteins.

Engineering Genetic Systems for Biotherapeutics and Biomaterials

"This study provides insights into the plasticity of genetic codes," said Farren Isaacs, professor of molecular, cellular, and developmental biology at Yale and co-senior author. "It also showcases our ability to engineer genetic systems to create multifunctional proteins, ushering in a transformative era for biotherapeutics and biomaterials."

Building on the 2013 GRO Study

This groundbreaking advancement builds upon the team's 2013 Science publication, which detailed the creations of the first genomically recoded organism (GRO). That study introduced novel strategies for enhancing the safety of genetically engineered organisms while enabling the production of synthetic proteins and biomaterials with artificial, human-designed chemistries.

Advancing Non-Redundant Genetic Code in E. coli

Ochre represents a significant advancement toward establishing a streamlined, non-redundant genetic code in E. coli, an organism well-suited for synthesizing proteins that incorporate multiple distinct synthetic amino acids.

Engineering the Genome - A New Scale of Innovation

Jesse Rinehart, associate professor at Yale School of Medicine and co-senior author, described the research as a groundbreaking demonstration of whole-genome engineering, achieving over 1,000 targeted edits-an innovation that significantly surpasses all previous genetic engineering milestones.

Unlocking Applications in Research and Industry

"This groundbreaking platform technology paves the way for a wide range of biotechnological applications across both academic research and commercial industries," said Rinehart. "Our goal is not only to expand scientific knowledge but also to drive industrial innovations that benefit society."

Understanding Codons and Their Role in Protein Engineering

What are Codons?

The codon, a three-nucleotide sequence found in DNA and RNA, functions as a genetic blueprint for protein synthesis. It instructs the cell on which of the 20 natural amino acids to integrate into a developing protein chain or, if a 'stop' codon is encountered, to cease synthesis. This process, known as translation, enables mRNA to regulate both the sequence of amino acids and the initiation and termination of protein formation.

Redefining the Genetic Code

Michael Grome, a postdoctoral associate in molecular, cellular, and developmental biology at Yale and first author of the study, compare codons to three-letter words in the genetic blueprint of life. He explained that within the cell, ribosomes function like 3D printers, interpreting this genetic code. Each codon specifies a single amino acid, selected from the 20 natural amino acids that form proteins.

Removing Redundancy to Expand Functionality

"Many of these codons are synonymous, meaning they convey the same instruction," explained Grome. "Our goal to expand the set of available building blocks for proteins. To achieve this, we consolidated three stop codons into one, effectively removing two and reprogramming the cell to repurpose them for new functions. We then engineered the cell to interpret these freed codons as instructions for incorporating novel amino acids."

AI-Guided Engineering for Synthetic Biology

The researchers strategically removed two to the three stop codons responsible for terminating protein synthesis. In the recoded genome, four codons were reassigned to novel, non-redundant roles, including the two modified stop codons, which were repurposed to encode nonstandard, or synthetic, amino acids within proteins.

Beyond implementing thousands of precise genomic edits, the study leveraged AI-driven desing and the re-engineering of key protein and RNA translation factors to develop a strain capable of incorporating two nonstandard amino acids into its genetic framework.

Expanding Functional Capabilities of Proteins

The incorporation of these nonstandard amino acids grants proteins novel functionalities, enabling the development of programmable biologics with reduced immunogenicity and biomaterials with enhanced elecrical conductivity.

A Decade-Long Collaboration in Genome Engineering

These findings represent the culmination of years of genome recoding research conducted by two laboratories at the Yale Systems Biology Institute on West Campus.

Complementary Expertise in Genome and Protein Engineering

The collaboration between Rinehart and Isaacs began in 2010 when they worked in adjacent labs. Isaacs, likening his work to architectural planning, has focused on genome engineering, while Rinehart's research centers on protein synthesis and their functional potential.

"We realized that our skill sets were complementary and that both labs contribute a diverse range of expertise and technical capabilities,' Rinehart stated.

Future Applications of Programmable Protein Biologics

Isaacs is enthusiastic about what he considers game-changing applications for programmable protein biologics enabled by this new platform.

One promising avenue involves designing protein-based therapeutics with synthetic chemistries to reduce dosing frequency and mitigate adverse immune responses.

Validating the Approach - The 2022 Study

The team previously demonstrated such an application in a 2022 study utilizing their first-generation GRO.

By incorporating non-standard amino acids into proteins, they introduced a safer and tunable approach to modulating the half-life of protein biologics.

Bringing Programmable Biologics to Market

The Ochre cell enhances these capabilities, enabling the development of multifunctional biologics. Isaacs and Rinehart currently serve as advisors to Pearl Bio, a Yale biotechnology spin-off that has secured licensing rights to commercialize programmable biologics.

Source


"Unlock the Future of Genetic Engineering!

Yale scientists have achieved a groundbreaking milestone in synthetic biology by recoding the genome to create programmable synthetic proteins. This revolutionary advancement paves the way for next-generation biopharmaceuticals, enhanced biomaterials, and novel protein-based therapeutics.

How will this impact medicine, biotech, and industrial applications?

Read the full story now!

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Saturday, February 1, 2025

ear muscle activation focused listening

New Research Reveals Ear Muscle Activates During Focused Listening

The Role of Auricular Muscles in Hearing

Ancestral Function and Vestigial Structures

Auricular muscles activated during listening tasks in new research, studying ear movement and focused auditory effort.

If you can move your ears, you're using muscles that helped our distant ancestors enhance their hearing. These auricular muscles would adjust the pinna's form, funneling sound waves directly to the eardrum.

Although our ancestors ceased relying on them millions of years ago, auricular muscles in humans remains as vestigial structures. However, recent research reveals that these muscles still activate when we focus on distinguishing competing sounds.

Insights from The Frontiers in Neuroscience Study

Andreas Schröer, first author of the Frontiers in Neuroscience study from Saarland University, explains that ear wiggling relies on three large muscles that connect the auricle to the skull and scalp.

These muscles, especially the superior auricular muscle, become more active during intense listening efforts, suggesting their role extends beyond reflexes to aiding attentional focus in challenging auditory conditions.

measuring Listening Effort

Electromyography and Auricular Muscle Activity

Quantifying listening effort remains difficult without self-reported measures. Yet, electromyography, which records muscle electrical activity, provides insight into auricular muscle function during attentive listening. Prior studies indicate that the posterior and superior auricular musclesresponsible for pulling the ears up and backactivate when an individual focuses on auditory stimuli. This suggests their ancestral role in pinna movement to optimize sound reception.

Hypotheses on Vestigial Function

"The exact caused of these muscles becoming vestigial remains unclear, given that our ancestors lost this function around 25 million years ago," Schröer noted. "A plausible hypothesis suggests that as human visual and vocal capabilities advanced, the selective pressure for ear mobility diminished."

Experimental Approach

Study Design and Conditions

Researchers examined whether auricular muscles exhibit heightened activity during complex listening conditions by enlisting 20 participants with no hearing impairments. Electrodes were affixed to their auricular muscles as they listened to an audiobook with distracting podcasts played from speakers positioned either in front or behind them. The experiment consisted of 12 five-minute trials, each varying in difficulty across three levels.

Adjusting Task Difficulty

In the Easiest Condition, the podcast was played at a lower volume than the audiobook with a clear distinction between the two voices. To increase difficulty researchers introduced a podcast that closely resembled the audiobook's tone and increased the volume of distracting audio. However, they ensured that even the most challenging condition remained achievableif participants disengaged no physiological effort could be measured.

Participant Feedback and Comprehension

Following each trial, participants were asked to assess their listening effort and estimate how frequently they lost track of the audiobook. Additionally, researchers tested their comprehension through content-related questions.

Key Findings and Implications

Distinct Muscle Responses

The researchers observed that the two auricular muscles exhibited distinct responses to varying conditions. While the posterior auricular muscles were sensitive to shifts in sound direction, the superior auricular muscles showed greater activation in response to the task's level of difficulty.

Self-reported effort levels and the frequency with which participants lost track of the audiobook increased with the task's difficulty. Additionally, accuracy in answering content-related questions significantly declined as the moved from moderate to high difficulty.

Superior Auricular Muscle as a Measure of Listening Effort

This findings aligned with the activity levels of the superior auricular muscles, which did not show increased activation during the medium mode compared to the easy mode, but were notably active during the difficult mode. This indicates that superior auricular muscle activity may serve as an objective measure of listening effort, though it remains unclear whether this muscle activity aids in hearing.

Evolutionary Considerations

"The ear movements induced by the recorded signals are subtle that any potential benefits are likely imperceptible," said Schröer.

While the auricle plays a role in sound localization, the auriculomotor system likely exerts its best effort after 25 million years of vestigial development, though its effectiveness is limited.

Future Directions and Research Needs

Further Studies and Practical Applications

The researchers emphasized that additional studies are needed to validate these findings and explore their practical applications. Like many auditory studies, their sample size was limited, consisting mostly of young, healthy individuals. To draw more robust conclusions, larger and more diverse participant groups, tested under more realistic conditions, are required.

Exploring Additional Impacts on Hearing

Schrö er stated, "In the future, we aim to explore the potential impact of muscle strain and the ear's minute movements on sound transmission."

"It would also be valuable to examine how these factors affect individuals with hearing impairments."

Source


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