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Biology

Uncovering the Secrets of Cellular Diversity: How Cancer Cells Respond to Stress in Real-Time

Cancer cells respond to stress with greater diversity. Drugs that affect DNA replication, or radiation that causes direct DNA damage, lead to increasingly diverse offspring over multiple cell generations. This increases the tumor’s genetic complexity and facilitates the development of resistance to therapy. Researchers have now investigated the emergence of cellular diversity in real time.

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Cancer cells are notorious for their ability to adapt and evolve, making them notoriously difficult to treat. A key factor in this resilience is their capacity for cellular diversity – the ability to generate new variations within a cell population. This diversity arises from genetic mutations that alter DNA sequences, as well as epigenetic changes that influence gene activity.

Researchers at the University of Zurich (UZH) have made significant strides in understanding how cancer cells develop and become increasingly diverse over multiple generations. Using CRISPR-based genome editing, they attached fluorescent markers to two proteins: one tracking DNA replication and the other marking acquired DNA damage. This allowed them to monitor, in real-time, how cancer cells respond to different stress factors and how this increases heterogeneity within the cell population.

The study revealed that daughter cells no longer behave synchronously after cell division if the mother cell was exposed to stress. Significant differences were found, for example, in the onset and duration of DNA replication and in the production of proteins regulating the cell cycle. These differences continued into the next cell generation, thus increasing heterogeneity within the cell population.

Moreover, the researchers observed that DNA damage and stress not only have short-term consequences but also long-term effects on cellular diversity. This increase in genetic complexity allows cells to adapt more quickly and develop resistance mechanisms against drugs.

Computer-assisted cell tracking provided direct insights into how polyploidy arises in cells. In this process, cancer cells receive multiple copies of the genome, increasing genetic complexity and facilitating the development of resistance to therapy.

The combination of real-time and endpoint measurements showed that different pathways towards polyploidy have distinct effects on the stability of the genome, thereby influencing cell fitness. This understanding can potentially be used to modulate the ways how polyploidy occurs and tailor therapies more effectively.

This study is the first to demonstrate in detail how different mechanisms influence genetic stability across multiple cell generations and increase heterogeneity between individual cells. The research team aims to further develop and automate this method, leveraging technology platforms at UZH to facilitate single-cell and complex heterogeneity analyses. As they conclude, “we currently only see the proverbial tip of the iceberg,” hinting at the vast potential for future research in this field.

Animals

Sugar-Based Sensors Revolutionize Snake Venom Detection

Researchers have published the first example of a synthetic sugar detection test for snake venom, offering a new route to rapid diagnosis and better antivenoms.

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The detection of snake venom is a crucial step in treating life-threatening snake bites. According to the World Health Organization (WHO), every five minutes, 50 people are bitten by a snake worldwide, resulting in four permanent disabilities and one death. Traditional methods for diagnosing snake venom rely on antibodies, which have limitations such as high costs, lengthy procedures, and inconsistencies.

Researchers at the University of Warwick have made a groundbreaking discovery that could revolutionize snake venom detection. They have developed a glycopolymer-based ultraviolet-visible (UV-vis) test to detect Western Diamondback Rattlesnake (Crotalus atrox) venom. This new assay is a cheap and rapid alternative to antibody-based approaches, showcasing a version that specifically detects Crotalus atrox venom.

Dr. Alex Baker, lead researcher of the Baker Humanitarian Chemistry Group, explained that snake venoms are complex, making it challenging to detect toxins in the body. However, their research has produced an assay using synthetic sugars that mimic the natural sugar receptors targeted by venom proteins. The team engineered synthetic chains of sugar-like units (glycopolymers) attached to gold nanoparticles to amplify the response and make the reaction visible.

The Western Diamondback Rattlesnake venom binds to specific sugar molecules on red blood cells and platelets, disrupting blood clotting or interfering with immune responses leading to disability and death. The new assay changes color when venom toxins bind to the synthetic sugars, providing a rapid and cheap detection method beyond antibody-based techniques.

Mahdi Hezwani, first author of the research paper, emphasized that this assay could be a game-changer for snake envenomation. The team tested venom from other snake species, such as the Indian Cobra (Naja naja), and found that it did not interact with glycans in the body. This suggests that the new assay may have potential to distinguish between different snake venoms based on their sugar-binding properties.

This is the first example of a diagnosis test using sugars for detecting snake venom in a rapid detection system, building on the work of the Warwick research group using a glyconanoparticle platform in COVID-19 detection. The new assay is faster, cheaper, and easier to store, making it a more practical solution for treating snake bites.

The University of Warwick’s STEM Connect programme has enabled this innovative research, demonstrating the potential for bold and innovative solutions in addressing global health challenges.

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Animal Learning and Intelligence

The Buzz on Caffeine: How it Affects the Sleeping Brain

Coffee can help you stay awake. But what does caffeine actually do to your brain once you’re asleep? Using AI, a team of researchers has an answer: it affects the brain’s ‘criticality’.

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The article delves into the intricate relationship between caffeine and the sleeping brain, offering fresh insights from a recent study published in Nature Communications Biology. Researchers from Université de Montréal have shed new light on how caffeine can modify sleep patterns and influence the brain’s recovery during the night.

Led by Philipp Thölke, a research trainee at UdeM’s Cognitive and Computational Neuroscience Laboratory (CoCo Lab), the team used AI and electroencephalography (EEG) to study caffeine’s effects on sleep. Their findings reveal that caffeine increases the complexity of brain signals and enhances brain “criticality” during sleep – a state characterized by balanced order and chaos.

Interestingly, this effect is more pronounced in younger adults, particularly during REM sleep, the phase associated with dreaming. The researchers attribute this finding to a higher density of adenosine receptors in young brains, which naturally decrease with age. Adenosine is a molecule that accumulates throughout the day, causing fatigue.

The study’s lead author, Thölke, notes that caffeine stimulates the brain and pushes it into a state of criticality, where it is more awake, alert, and reactive. However, this state can interfere with rest at night, preventing the brain from relaxing or recovering properly.

The researchers used EEG to record the nocturnal brain activity of 40 healthy adults on two separate nights: one when they consumed caffeine capsules three hours before bedtime and another when they took a placebo at the same time. They applied advanced statistical analysis and artificial intelligence to identify subtle changes in neuronal activity, revealing that caffeine increased the complexity of brain signals during sleep.

The team also discovered striking changes in the brain’s electrical rhythms during sleep: caffeine attenuated slower oscillations such as theta and alpha waves – generally associated with deep, restorative sleep – and stimulated beta wave activity, which is more common during wakefulness and mental engagement.

These findings suggest that even during sleep, the brain remains in a more activated, less restorative state under the influence of caffeine. This change in the brain’s rhythmic activity may help explain why caffeine affects the efficiency with which the brain recovers during the night, with potential consequences for memory processing.

The study’s implications are significant, particularly given the widespread use of caffeine as a daily remedy for fatigue. The researchers stress the importance of understanding its complex effects on brain activity across different age groups and health conditions. They add that further research is needed to clarify how these neural changes affect cognitive health and daily functioning, potentially guiding personalized recommendations for caffeine intake.

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Biology

Unraveling Microtubule Mysteries: Scientists Crack Code on Cellular Scaffolding Secrets

Scientists found out how naturally unstable filaments decide whether to grow or to shorten.

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A groundbreaking study has shed new light on the fundamental mechanisms governing microtubule growth within cells. Researchers from Queen Mary University of London and the University of Dundee have made a significant breakthrough by discovering that the ability of tubulin proteins at microtubule ends to connect with each other sideways determines whether a microtubule elongates or shortens.

Microtubules are crucial protein structures that form the internal skeleton of cells, providing structural support and generating dynamic forces that push and pull. These tiny filaments constantly assemble and disassemble by adding or removing tubulin building blocks at their ends. However, the precise rules dictating whether a microtubule grows or shrinks have long remained a mystery due to the complexity and miniature size of their ends.

The collaborative research team has cracked part of this code using advanced computer simulations coupled with innovative imaging techniques. This interdisciplinary approach has allowed them to address this complex biological question from a fresh perspective, bridging physics and biology.

Dr. Vladimir Volkov, co-lead author from Queen Mary University of London, explained the significance of their findings: “Understanding how microtubules grow and shorten is very important – this mechanism underlies division and motility of all our cells. Our results will inform future biomedical research, particularly in areas related to cell growth and cancer.”

Dr. Maxim Igaev, co-lead author from the University of Dundee, highlighted the power of their interdisciplinary approach: “Bridging physics and biology has allowed us to address this complex biological question from a fresh perspective. This synergy not only enriches both fields but also paves the way for discoveries that neither discipline could achieve in isolation.”

This exciting research deepens our understanding of fundamental cellular processes and opens potential new avenues for biomedical research, particularly in areas concerning cell proliferation and the development of treatments for diseases like cancer.

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