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CRISPR, regenerative medicine, vaccine development and recombinant DNA tech Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Medical Biotechnology 10/07/25, 10:21 Last updated: Published: 03/06/23, 13:57 CRISPR, regenerative medicine, vaccine development and recombinant DNA tech Introduction Throughout the course of human history, the foundation of medicine has predominantly relied upon biochemistry. Whereby, scientists utilise naturally occurring and artificially synthesised chemical compounds to elicit therapeutic responses within the body. However, during the 21st century, the field of medicine witnessed a paradigm shift towards medical biotechnology- driving major breakthroughs in healthcare. What is medical biotechnology? Medical biotechnology can be defined as the use of living organisms or their products to investigate, understand and target biological systems in order to improve healthcare outcomes. By integrating the principles of genetic engineering and biological processes, scientists are able to develop novel pharmaceuticals and create diagnostic tools for disease management. Major advancements in medical biotechnology A groundbreaking technology within this field is the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) — Cas9 system. Which utilises CRISPR-associated protein Cas9 and guide RNA (gRNA) as a molecular tool to precisely modify genetic material. By harnessing this gene editing system, scientists can manipulate specific DNA sequences and modulate gene expression, making it an invaluable tool towards precision medicine. Its ability to correct genetic defects has shown promise in the future development of targeted therapies for genetic diseases. Regenerative medicine, another frontier in medical biotechnology aims to regenerate damaged or diseased tissues and organs. This interdisciplinary field integrates principles from tissue engineering and stem cell biology to enable tissue repair and regeneration. Stem cells possess a remarkable capacity to self-renew and differentiate into various specialised cell types. Through research biotechnologists seek to engineer functional tissues and organs for transplantation or stimulate the body's innate regenerative abilities. The development of vaccines is yet another critical aspect of medical biotechnology. Vaccines are designed to stimulate the immune system and confer immunity against specific pathogens, thereby preventing infectious diseases. Modern biotechnology techniques, such as genetic engineering and cell culture, enable cost-effective vaccine development. Recombinant DNA technology enables antigen production in non-pathogenic host cells, eliminating the need for pathogen harvesting. Ongoing advancements include RNA/DNA vaccines, allowing antigen production within recipients' bodies. Conclusion Medical biotechnology continues to play a pivotal role in advancing scientific knowledge and enhancing disease diagnostics and treatment. It holds immense promise for the future of healthcare, particularly in the field of precision medicine. However, it is crucial to acknowledge that this technology also carries inherent risks. Misuse can lead to negative consequences, such as bioterrorism and other destructive outcomes. Written by Komal Nasir Related article: Biggest innovations in the biosciences currently Project Gallery

Ways in which pathogens avoid being detected by the immune system Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Mechanisms of pathogen evasion 27/03/25, 11:23 Last updated: Published: 05/09/24, 10:54 Ways in which pathogens avoid being detected by the immune system Introduction Pathogens such as bacteria and viruses have evolved strategies to deceive and outsmart the immune system's defences. From hiding within cells to avoiding immune detection to blocking signals crucial for immune function, pathogens have developed an array of tactics to stay one step ahead of the immune system. This article introduces some key strategies pathogens employ to evade the immune system. Antigenic variation The influenza virus is a persistent and challenging pathogen to treat because it employs a clever strategy known as antigenic variation to evade the immune system. Antigenic variation is the pathogen’s ability to alter the proteins on its surface (antigens), particularly hemagglutinin (HA) and neuraminidase (NA), which are the primary targets of the immune system. As the virus conceals itself, it is no longer recognised and attacked by the host's defences. But how do the surface antigens change? This occurs through two primary mechanisms: antigenic drift and antigenic shift. The former process involves gradual changes in the virus's surface proteins by progressive accumulation of genetic mutations. Meanwhile, the latter requires a slightly different explanation. Antigenic shift is an abrupt process. It occurs when two influenza virus strains infect the same host cell and exchange genetic material. The exchange can lead to a new hybrid strain. This hybrid strain usually presents a new combination of surface proteins. It is a more abrupt process, and because the immune system lacks prior exposure to these new proteins, it fails to clear the viral pathogen. Antigenic shifts can lead to the emergence of strains to which the population has little to no pre-existing immunity. Some examples are the 1968 Hong Kong flu and the 2009 swine flu pandemic. Variable serotypes- Streptococcus pneumoniae When the host encounters a pathogen, the body creates antibodies against specific proteins on the pathogen's surface, ensuring long-term immunity. However, some species of pathogens evade this protection by evolving different strains. These strains involve multiple serotypes, each defined by distinct variations in the structure of their capsular polysaccharides. This variability allows them to infect the same host repeatedly, as immunity to one serotype does not confer protection against other serotypes. A perfect example of such a pathogen is the pneumonia-causing bacterium, Streptococcus pneumoniae , which has more than 90 strains. After successful infection with a particular S. pneumoniae serotype, a person will have devised antibodies that prevent reinfection with that specific serotype. However, these antibodies do not prevent an initial infection with another serotype, as illustrated in Figure 1 . Therefore, by evading the immune response, a new primary immune response is required to clear the infection. Latency- chicken pox & Human Immunodeficiency Virus (HIV) Pathogens can cleverly persist in the host by entering a dormant state where they are metabolically inactive. In this state, they are invisible to the immune system. Human Immunodeficiency Virus is well known for its use of HIV latent reservoirs. These reservoirs, consisting of metabolically inactive T-cells infected with HIV, can exist for years on end. When the host becomes immunocompromised at any stage in life, the T-cells in these reservoirs are suddenly activated to renew HIV production. The Varicella-Zoster Virus (VZV) is responsible for causing varicella (chickenpox) and zoster (shingles). Similarly, this virus can remain latent in the host to evade immune detection. VZV establishes latency in sensory ganglia, particularly in neurons. Since neurons are relatively immune-privileged sites, they are less accessible to immune surveillance mechanisms. This provides a safe haven from immune detection. When the host is immunocompromised, the virus reactivates. This renewed viral activity results in the production of viral particles which travel along the sensory nerve fibres towards mucous membranes. When the virus reaches the skin, it causes an inflammatory response. This results in painful vesicular skin lesions, commonly known as shingles (herpes zoster). Conclusion Pathogens employ diverse mechanisms to evade the host immune system, ensuring their survival and propagation through host cells. These evasion mechanisms can hinder the development of treatments for certain infectious diseases. For instance, the diversity in Strep A serotypes challenges vaccine development because immunity to one serotype may not confer protection against another. Additionally, the influenza virus constantly evolves via antigenic variation, always one step ahead of the immune system. The strategies employed by pathogens to evade the immune system are as diverse as they are sophisticated. Scientists continue to study these mechanisms, paving the way for developing more effective vaccines, treatments, and public health strategies to out-manoeuvre these organisms. We can better protect human health by staying one step ahead of pathogen evolution. Written by Fozia Hassan Related articles: Allergies / Plant diseases REFERENCES Abendroth, Allison, et al. “Varicella Zoster Virus Immune Evasion Strategies.” Current Topics in Microbiology and Immunology , 2010, pp. 155–171, www.ncbi.nlm.nih.gov/pmc/articles/PMC3936337/ , https://doi.org/10.1007/82_2010_41 . Accessed 24 July 2024. Gougeon, M-L. “To Kill or Be Killed: How HIV Exhausts the Immune System.” Cell Death & Differentiation , vol. 12, no. S1, 15 Apr. 2005, pp. 845–854, www.nature.com/articles/4401616 , https://doi.org/10.1038/sj.cdd.4401616 . Accessed 24 July 2024. Parham, Peter. The Immune System . 5th ed., New York, Garland Science, 2015, read.kortext.com/reader/epub/1743564 . Accessed 24 July 2024. Shaffer, Catherine. “How HIV Evades the Immune System.” News-Medical.net , 21 Feb. 2018, www.news-medical.net/life-sciences/How-HIV-Evades-the-Immune-System.aspx . Accessed 24 July 2024. Project Gallery

AI in developing different space technologies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Artificial intelligence in space 11/04/26, 14:03 Last updated: Published: 19/11/23, 17:31 AI in developing different space technologies Artificial intelligence or AI has become an important force or a tool that drives the evolution of technologies that improve human life and helps unlock the secrets of the universe beyond the influence of our planet. In simple words, AI is something that enables a computer/ robot to mimic human intelligence and it is revolutionizing the way we explore and utilise space, enhancing everything from spacecraft navigation and autonomous decision-making to data analysis and mission planning. This article explores the profound impact of AI in the development of space related technologies. Mission planning and design Space mission planning and payload, instrument designs rely on the gathered previous mission data. However, access to all the historic mission data is only provided to individuals with a higher authority access at the space agency which requires a lot of paper works and approvals. But recently NASA came up with a solution and they named it as the “Data Acquisition Processing and Handling Network Environment” (DAPHNE) system. Daphne-AT is an AI assistant that can access millions of previous mission data including the most restricted ones and provide the scientists an insight about their mission without the need of a higher authority access or security clearance. It can also compute and analyse countless input variables to determine the most efficient routes and schedules for missions, which is crucial for long-duration missions or missions with multiple objectives. Manufacturing Manufacturing processes usually involves complex tasks that requires high precision and attention to detail when it comes to space related applications. The use of AI in spacecraft manufacturing not only accelerates production but also increases precision and reliability. AI assistants like collaborative bots (cobots) interact with the engineers and help them to make the right decisions, reduce the overall assembly process time, and also provide insights about the final product which ensures that the spacecrafts are built to the highest standards. Data processing Space missions generate vast amounts of data, from images and telemetry to instrument readings. AI algorithms are capable in sifting through this data, identifying patterns, and extracting meaningful insights. An example is the estimation of planetary wind speed which requires a combination of the satellite imagery and meteorological data. AI tools can rapidly analyse these large datasets and help scientists in understanding these planetary phenomena and easily uncover its secrets. This capability is also valuable in missions to study distant galaxies, black holes, and exoplanets. Navigation & guidance systems One of the critical applications of AI in space technology is autonomous navigation. Spacecraft traveling vast distances through the cosmos must constantly adjust their trajectories to avoid collisions with celestial bodies and maximise their fuel efficiency. Advanced AI systems can process data in real-time and autonomously adjust a spacecraft's course. This not only reduces the need for constant human intervention from the ground station but also allows for more precise and efficient missions. Astronaut health monitoring Astronauts in space face a range of health issues like bone density loss, cardiovascular issues etc. The AI systems can continuously monitor physiological data and provide an insight into the astronaut’s health condition including sleep patterns. This allows early detection of health issues and timely intervention which reduces the need for immediate communication with ground mission control, ultimately safeguard the safety of the astronauts on long-duration missions. In summary, AI is a tool that represents a transformative shift in how we explore and understand our cosmos and its secrets. One day, AI will play an even more significant role that pushes the boundaries of space and bring us closer to answering some of humanity’s most profound questions. Written by Arun Sreeraj Related articles: Astronauts in space / AI in drug discovery / Evolution of AI / Chemistry in space exploration Project Gallery

The chemistry that makes plastics strong also makes them extremely resistant to deterioration Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Plastics and their environmental impact: a double-edged sword 10/07/25, 10:29 Last updated: Published: 06/11/24, 12:25 The chemistry that makes plastics strong also makes them extremely resistant to deterioration Plastics have become an indispensable part of modern life. They are found in everything from electronics and packaging to construction materials and medical equipment. These multipurpose materials, mostly derived from petrochemicals, are successful because they are inexpensive, lightweight, and long-lasting. However, one of the biggest environmental problems of our time is their resilience, which makes them so beneficial. The chemistry that makes plastics strong also makes them extremely resistant to deterioration, which causes environmental damage and widespread contamination. The chemistry behind plastics Most plastics are composed of polymers, which are lengthy chains of monomers—repeating molecular units. Depending on how the molecules are arranged and the chemical additives added during synthesis, these polymers can be made to have a variety of characteristics, including stiffness or flexibility. Hydrocarbons from natural gas or crude oil are polymerised to create common plastics like polypropylene, which is used in food containers, and polyethene, which is used in plastic bags. While these plastics are ideal for their intended purposes —protecting products, storing food, and more, they are extremely resistant to degradation. This is due to their stable carbon-carbon bonds, which natural organisms and processes find difficult to break down. As a result, plastics can remain in the environment for hundreds of years, breaking down into tiny bits rather than entirely dissolving. See Figure 1 . The problem of micro-plastics Plastics in the environment degrade over time into tiny fragments known as microplastics, which are defined as particles smaller than 5 mm in diameter. These microplastics originate from a variety of sources, including the breakdown of larger plastic debris, microbeads used in personal care products, synthetic fibres shed from textiles and industrial processes. They are now widespread in every corner of the globe, from the deepest parts of the oceans to remote mountain ranges, the air we breathe, and even drinking water and food. Microplastics are particularly problematic in marine environments. Marine animals such as fish, birds, and invertebrates often mistake microplastics for food. Once ingested, these particles can accumulate in the animals' digestive systems, leading to malnutrition, physical damage, or even death. More concerning is the potential for these plastics to work their way up the food chain. Predators, including humans, may consume prey that has ingested microplastics, raising concerns about the potential effects on human health. Recent studies have detected microplastics in various human-consumed products, including seafood, table salt, honey, and drinking water. Alarmingly, microplastics have also been found in human organs, blood, and even placentas, highlighting the pervasive nature of this contamination. While the long-term environmental and health effects of microplastics are still not fully understood, research raises significant concerns. Microplastics can carry toxic substances such as persistent organic pollutants (POPs) and heavy metals, posing risks to the respiratory, immune, reproductive, and digestive systems. Exposure through ingestion, inhalation, and skin contact has been linked to DNA damage, inflammation, and other serious health issues. Biodegradable plastics: a possible solution? One possible solution to plastic pollution is the development of biodegradable plastics, which are engineered to degrade more easily in the environment. These plastics can be created from natural sources such as maize starch or sugarcane, which are turned into polylactic acid (PLA), or from petroleum-based compounds designed to disintegrate more quickly. However, biodegradable polymers do not provide a perfect answer. Many of these materials require certain circumstances, such as high heat and moisture, to degrade effectively. These conditions are more commonly encountered in industrial composting plants than in landfills or natural ecosystems. As a result, many biodegradable plastics can remain in the environment if not properly disposed of. Furthermore, their production frequently necessitates significant quantities of energy and resources, raising questions about whether they are actually more sustainable than traditional plastics. Innovations in plastic recycling Given the limitations of biodegradable polymers, improving recycling technology has become the main issue in the battle against plastic waste. Traditional recycling methods, like mechanical recycling, involve breaking down plastics and remoulding them into new products. However, this process can degrade the material's quality over time. However, this may compromise the material's quality over time. Furthermore, many types of plastics are difficult or impossible to recycle due to variances in chemical structure, contamination, or a lack of adequate machinery. Recent advances have been made to address these issues. Chemical recycling, for example, converts plastics back into their original monomers, allowing them to be re-polymerised into high-quality plastic. This technique has the ability to recycle materials indefinitely without compromising functionality. Another intriguing technique is enzymatic recycling, in which specially built-enzymes break down plastics into their constituent parts at lower temperatures, reducing the amount of energy required for the process. While these technologies provide hope, they are still in their early phases of development and face significant economic and logistical challenges. Expanding recycling infrastructure and developing more effective ways are critical to reduce the amount of plastic waste entering the environment. The way forward The environmental impact of plastics has inspired a global campaign to reduce plastic waste. Governments, industry, and consumers are taking action by prohibiting single-use plastics, increasing recycling efforts, and developing alternatives. However, addressing the plastic problem necessitates a multifaceted strategy. This includes advances in material science, improved waste management systems, and, perhaps most crucially, a transformation in how we perceive and utilise plastics in our daily lives. The chemistry of plastics is both fascinating and dangerous. While they have transformed businesses and increased quality of life, their long-term presence in the environment poses a substantial risk to ecosystems and human health. Rethinking how we make, use, and discard plastics in order to have a more sustainable relationship with these intricate polymers may be more important for the future of plastics than just developing new materials. Written by Laura K Related articles: Genetically-engineered bacteria break down plastic / The environmental impact of EVs Project Gallery

The slippery property of a superfluid is caused by its ability to flow very easily Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The incredibly slippery nature of superfluids 03/04/25, 10:33 Last updated: Published: 24/05/23, 08:53 The slippery property of a superfluid is caused by its ability to flow very easily Slipperiness is a property that we often associate with everyday objects like ice, soap, and banana peels. However, there is a substance that is even more slippery than these: superfluids. A normal liquid becomes a superfluid when it is cooled down below a certain temperature. This temperature is unique to all fluids, for example for helium it is 2.17 K. Below this temperature, the superfluid will behave in completely unique ways. For example, if a container of water at room temperature was spun, you’d expect the water to also spin around, creating a whirlpool. Whereas a superfluid in a spinning container doesn’t spin at all, until it reaches a certain speed! The slippery property of a superfluid is caused by its ability to flow very easily. Usually it’s safe to leave a glass of water on a countertop (unless of course you’ve got a particularly excitable dog), but if you were to leave a glass of superfluid on a table, the liquid would creep out and escape. The tiny changes in temperature or pressure in the container cause it to flow, seemingly defying gravity. Unfortunately, superfluids cannot just be bought in the local supermarket! To produce a superfluid, devices known as cryostats can be used to cool a substance down to low temperatures. Using the ideal gas model, pressure, and volume can be related, so by reducing the pressure, the temperature of the device can also be decreased. The pressure is reduced using a vacuum pump, which works by removing particles from the cryostat. The applications of superfluids are limited as, due to the typically very low temperatures needed for a normal fluid to transition to a superfluid, there is difficulty in producing superfluids. Currently, scientists are working on finding fluids that enter a stable superfluid state at room temperatures. However, superfluids are used within many fields of physics to explain certain phenomena. One theory is that the core of collapsed large stars (neutron stars) is a superfluid, despite the very hot temperatures. The idea is that below a certain temperature, it uses less energy for the core to behave like a superfluid which cools the star down at an increased rate. The superfluid theory of neutron stars is just a hypothesis, however hints at the role superfluids play in all areas of physics. Written by Madeleine Hales REFERENCES/ FURTHER READING: https://www.aps.org/publications/apsnews/200601/history.cfm#:~:text=In%201927%20Willem%20Keesom%20and,helium%20I%20and%20helium%20II . https://physicsworld.com/a/neutron-star-has-superfluid-core/ Project Gallery

Total solar eclipses Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Totality- Our Perfect Eclipse 14/07/25, 15:05 Last updated: Published: 24/05/23, 10:05 Total solar eclipses We are all familiar with the characteristic depiction of a solar eclipse, when the Moon passes directly between the Sun and the Earth. However, the significance of solar eclipses extends far beyond their aesthetic appeal. Major scientific discoveries, cultural practices, and even the behaviour of wild animals are derived from total solar eclipses that we have the privilege of experiencing (See image 1). A solar eclipse occurs when the Earth, Moon, and Sun all appear to lie on a straight line. They are collinear. Total solar eclipses occur when the Moon completely obscures the Sun's photosphere, enabling prominences and coronal filaments to be seen along the limb. This phenomenon is unique to the Earth, Sun, and Moon system and to understand why we must explore the mathematics underlying these ‘orbital gymnastics’. We wish to compare the ‘apparent’ size of the Sun and Moon, a quantity proportional to the ratio of their size and distance from Earth. The Moon has a radius of around 3,400 km, and is approximately 384,000 km from Earth. The Sun has a much larger radius of 1.4 million km, and is located at a distance of 150 million km. By dividing the Sun's radius by the Moon's radius and dividing the Earth-Sun distance by the Earth-Moon distance, we can determine that the Sun is 400 times larger than the Moon and 400 times further away. This unique relationship allows for total solar eclipses, where totality indicates **the complete blocking of sunlight from the Sun’s disk by the Moon. In partial eclipses, only part of the Sun is obscured. One might wonder why we don’t have total solar eclipses every month, and the reason is that the plane of the Moon’s orbit around Earth is tilted at 5 degrees relative to Earth’s orbital plane. This hugely decreases the likelihood of such perfect alignment. Of the hundreds of moons orbiting planets in our Solar System, only our Moon totally eclipses the Sun. For example, none of Jupiter’s 95 moons have the correct size and orbital separation that completely block out the Sun from any point on Jupiter’s surface! Surely this serendipitous interplay of Earth, Sun, and Moon cannot be a coincidence? (See image 2) It is at this point where divine intervention is typically invoked. There are a few problems with doing this. The Moon's eccentric orbit around Earth means that it will be closer during some total solar eclipses than others, resulting in annular eclipses when the Moon is furthest from Earth. Additionally, the Moon is receding from the Earth at a rate of 4 cm/year, which means that total solar eclipses will only be observable for another 250 million years. (See image 3) For those of you who wish to make the most of this brief window of opportunity, this website shows the dates and locations of upcoming total solar eclipses. Written by Joseph Brennan REFERENCE Guillermo Gonzalez, Wonderful eclipses, Astronomy & Geophysics , Volume 40, Issue 3, June 1999, Pages 3.18–3.20, https://doi.org/10.1093/astrog/40.3.3.18 Project Gallery

Peering into the mind Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Neuroimaging and spatial resolution 10/07/25, 10:24 Last updated: Published: 04/11/24, 14:35 Peering into the mind Introduction Neuroimaging has been at the forefront of brain discovery ever since the first ever images of the brain were recorded in 1919 by Walter Dandy, using a technique called pneumoencephalography (PET). Fast-forward over a decade and neuroimaging is more than just blurry singular images. Modern techniques allow us to observe real time changes in brain activity with millisecond resolution, leading to breakthroughs in scientific discovery that would not be possible without it. Memory is a great example - with functional magnetic resonance imaging (fMRI) techniques we have been able to demonstrate that more recent long-term memories are stored and retrieved with brain activity in the hippocampus, but as memories become more in the distant past, they are transferred to the medial temporal lobe. While neuroimaging techniques keep the doors open for new and exciting discoveries, spatial limitations leave many questions unanswered, especially at a cellular and circuit level. For example - within the hippocampus, is each memory encoded via complete distinct neural circuits? Or do similar memories share similar neural pathways? Within just a millimetre cubed of brain tissue we could have up to 57,000 cells (most of them neurons), all of which may have different properties, be part of different circuits, and produce different outcomes. This almost makes revolutionary techniques such as fMRI, with almost unparalleled image quality, seem pointless. To truly understand how neural circuits work, we have to dig as deep as possible to record the smallest regions possible. So that begs the question, how small can we actually record in the human brain? EEG 2024 marks a decade since the first recorded electroencephalography (also known as EEG) scan by Hans Berger in Germany. This technique involves placing electrodes all around the scalp to record activity throughout the whole outer surface of the brain ( Figure 1 ). Unlike the methods we see later on, EEG scans provide a direct measure of activity in the brain, by measuring electrical activity when the brain is active. However, because electrodes are only placed across the scalp, EEG scans are only able to pick up activity from the outer cortex, missing important activity in deeper parts of the brain. In our memory example, this means it would completely miss any activity in the hippocampus. EEG resolution is also quite underwhelming, typically being able to resolve activity with a few centimetres’ resolution - not great for mapping behaviours to specific structures in the brain. EEG scans are used in a medical environment to measure overall activity levels, assisting with epilepsy diagnosis. Let's look at what we can use to dig deeper into the brain and locate signals of activity… PET Position emission tomography (PET) scans offer a chance to record activity throughout the whole brain by ingesting a radioactive tracer, typically glucose labelled with a mildly radioactive substance. This tracer is tracked and uptake in specific parts of the brain is a sign for greater metabolic activity, indicating a higher signalling rate. PET scans already offer a resolution far beyond the capacities of EEG scans, distinguishing activity between areas with a resolution of up to 4mm. With the use of different radioactive labels, we can also detect activity of specific populations of neurons such as dopamine neurons to diagnose Parkinson's disease. In fact, many studies have reliably demonstrated the ability of PET scans to detect the root cause of Parkinson's disease, which is a reduced number of dopamine neurons in the basal ganglia, before symptoms become too extreme. As impressive as it sounds, a 4mm resolution can locate activity in large areas of the cortex, but is limited in its resolving power for discrete cortical layers. Take the human motor cortex for example - all 6 layers have an average width of only 2.79mm. A PET scan would not be powerful enough to determine which layer is most active, so we need to dig a little deeper… fMRI Since its inception in the early 90's, fMRI has gained the reputation of becoming the gold standard for human neuroimaging, thanks to its non-invasiveness, lack of artefacts, and reliable signalling. fMRI uses Nuclear Magnetic Resonance to measure changes in oxygenated blood flow, which is correlative of neural activity, known as BOLD signals. In comparison to EEG, measuring blood oxygen levels cannot reach a highly impressive temporal resolution, and is also not a direct measure of neural activity. fMRI makes up for this with its superior spatial resolution, resolving spaces as small as 1mm apart. Using our human motor cortex example, this would allow us to resolve activity between every 2-3 layers - not a bad return considering it doesn’t even leave a scar. PET, and especially EEG, pales in comparison to the capabilities of fMRI that has since been used for a wide range of neuroimaging research. Most notably, structural MRI has been used to support the idea of hippocampal involvement during spatial navigation from memory tasks ( Figure 2 ). Its resolving power and highly precise images also make it suitable to be used for mapping surgical procedures. Conclusion With a resolution of up to 1mm, fMRI takes the crown as the human neuroimaging technique with the best spatial resolution! Table 1 shows a brief summary of each neuroimaging method. Unfortunately though, there is still so much more we need to do to look at individual circuits and connections. As mentioned before, even within a millimetre cubed of brain, we have 5 figures worth of cells, making the number of neurons that make up the whole brain impossible to comprehend. To observe the activity of a single neuron, we would need an imaging technique with the power of viewing cells in the 10’s of micrometre range. So what can we do to get to the resolution we desire while still being suitable for humans? Maybe there isn't a solution. Instead, maybe if we want to record singular neuron activity, we have to take inspiration from invasive animal techniques such as microelectrode recordings. Typically used in rats and mice, these can achieve single-cell resolution to look at neuroscience from the smallest of components. It would be unethical to stick an electrode into a healthy human's brain and record activity, but perhaps in the future a non-invasive form of electrode recording could be developed? The current neuroscience field is foggy and shrouded in mystery. Most of these mysteries simply cannot be solved with the current research techniques we have at our disposal. But this is what makes neuroscience exciting - there is still so much to explore! Who knows when we will be able to map behaviours to neural circuits with single-cell precision, but with how quickly imaging techniques are being enhanced and fine-tuned, I wouldn't be surprised if it's sooner than we think. Written by Ramim Rahman Related articles: Neuromyelitis optica / Traumatic brain injuries REFERENCES Hoeffner, E.G. et al. (2011) ‘Neuroradiology back to the future: Brain Imaging’, American Journal of Neuroradiology, 33(1), pp. 5–11. doi:10.3174/ajnr.a2936. Maguire, E.A. and Frith, C.D. (2003) ‘Lateral asymmetry in the hippocampal response to the remoteness of autobiographical memories’, The Journal of Neuroscience, 23(12), pp. 5302–5307. doi:10.1523/jneurosci.23-12-05302.2003. Wong, C. (2024) ‘Cubic millimetre of brain mapped in spectacular detail’, Nature, 629(8013), pp. 739–740. doi:10.1038/d41586-024-01387-9. Butman, J. A., & Floeter, M. K. (2007). Decreased thickness of primary motor cortex in primary lateral sclerosis. AJNR. American journal of neuroradiology, 28(1), 87–91. Loane, C., & Politis, M. (2011). Positron emission tomography neuroimaging in Parkinson's disease. American journal of translational research, 3(4), 323–341. Maguire, E.A. et al. (2000) ‘Navigation-related structural change in the hippocampi of taxi drivers’, Proceedings of the National Academy of Sciences, 97(8), pp. 4398–4403. doi:10.1073/pnas.070039597. [Figure 1] EEG (electroencephalogram) (2024) Mayo Clinic . Available at: https://www.mayoclinic.org/tests-procedures/eeg/about/pac-20393875 (Accessed: 18 October 2024). [Figure 2] Boccia, M. et al. (2016) ‘Direct and indirect parieto-medial temporal pathways for spatial navigation in humans: Evidence from resting-state functional connectivity’, Brain Structure and Function, 222(4), pp. 1945–1957. doi:10.1007/s00429-016-1318-6. Project Gallery

The rabies virus infects neurons Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Rabies- the scariest disease ever? 13/06/26, 15:29 Last updated: Published: 10/10/24, 11:05 The rabies virus infects neurons Rabies is a viral disease that primarily affects the central nervous system (CNS), usually in mammals. Wild animals such as foxes, dogs, and raccoons are frequent carriers of the virus. Transmission occurs through the saliva of an infected animal through a bite or a scratch, allowing the virus to enter the body and travel through the nervous system toward the brain. While rabies can be prevented with a vaccine (the latest one, ChAdOx2 RabG, is single-shot), once symptoms begin to show, the disease is nearly always fatal once symptoms begin to show. What makes this virus so deadly, and how can it take control of the human body with just five genes in its genome? Why is the virus so hard to kill? To arrive at a sensible answer, we must first understand the ‘tropism’ of the virus – the cell type it likes to infect. Rabies virus infects the neurones (neurotropic), which creates a massive problem for the immune system. Macrophages and neutrophils, which are the prominent cells in killing foreign pathogens that kill foreign pathogens, usually deal collateral damage to the body’s own cells to some extent. This must be avoided with neurones, as neurones cannot replenish themselves after cell death. An inflammation of the nerve cells could lead to paralysis and seizures, compromising the CNS. As a result, the immune system response is significantly lowered around nerve cells to prevent accidental damage, which allows the virus to infect the neural pathway easily. Transmission of the virus See Figure 1 The strategy of the immune system is that the neurones can be protected if the pathogens are intercepted before they travel to their destination. However, this strategy ultimately fails when it comes to rabies, because the transmission is through a bite, which can penetrate and cut through many layers of tissue, providing a direct access to nerve cells. If you were bitten on the leg, then the time it takes for the rabies virus to travel to your brain would be the time it takes for you to travel from Florida, USA to Sweden. This may seem like a long time, but the rabies virus has evolved a technique that is able to hijack the cellular transport system can trick your cells’ transport system to travel quickly through the nerves by binding to a protein called dynein . Dynein is a motor protein that move along the microtubules in cells, converting the chemical energy of ATP into mechanical work. Microtubules are polarized structures, with a plus end (typically towards the axon terminal in neurones) and a minus end (towards the cell body). Dynein moves toward the minus end, facilitating retrograde transport, meaning it moves materials from the periphery of the cell, such as the axon terminals, back toward the cell body. Dynein is transports chemicals inside cells via endocytosis and plays a vital role in the movement of eukaryotic flagella. Rabies has evolved to stick to dynein via the Glycoprotein (G) present on its viral envelope, which allows rabies to travel to the brain much quicker. Dynein may be small, weighing around two megadaltons (3 x 10-18 grams), but it can move at a speed of 800 nanometres per second. At this speed, it takes rabies around 14 days to move up a metre- long neuron. This implies that the closer the animal bites you to the brain, the less time it takes for the symptoms to appear. If you’re bitten on the foot, it could take months for the virus to reach your brain. But if you’re bitten on the neck or face, the virus can get to your brain in just a few days, making it much more dangerous. This explains the broad range in the incubation time which is between 20 to 90 days. Infection and replication- see Figure 2 As the rabies travels through neuronal tracks, it sets up points of concentrated viral production centres called Negri bodies. These replicate the rabies virus within the neurones and inhibit interferon action, which are chemicals that alert white blood cells to the area of infection. Interferon inhibition along with lowered immune response to neurones make rabies extremely effective. However, neurones can undergo apoptosis—controlled cell death—to limit the spread of the virus and allow macrophages to clear the debris. Research in mice suggests that some strains of rabies may prevent this apoptotic response in cells. Additionally, studies indicate that rabies promotes apoptosis in killer T cells, which are responsible for inducing apoptosis in other cells. This mechanism helps to shield nerve cells from immune system attacks. Symptoms Patients with rabies initially experience flu-like symptoms and muscle pain. Once these early symptoms appear, treatment is virtually impossible. As the disease progresses, neurological symptoms develop including hydrophobia due to painful throat spasms when swallowing liquids. About 10 days after these neurological symptoms start, patients enter a coma, often accompanied by prolonged sleep apnoea. As virus attacks the brain throughout this stage, patients develop the urge to bite other organisms to transmit the virus. The virus can reach the salivary glands, allowing for transmission through a bite to occur again. Most patients typically die within three days of reaching this coma stage. Legends Rabies may have influenced the development of vampire and zombie myths due to its distinct symptoms. The disease causes aggression and sensitivity to light, which could have inspired some characteristics of vampires, such as their aversion to light and erratic movements. Additionally, rabies leads to excessive salivation and a tendency to bite, traits that align with vampire lore. Similarly, the delirium and motor dysfunction seen in rabies may have contributed to the depiction of zombies as shuffling, incoherent beings. Conclusion Rabies is a uniquely deadly virus due to its mechanism of hijacking the nervous system. After entering the body, the virus binds to dynein, using it to travel along neuronal pathways toward the brain. It replicates rapidly, forming Negri bodies disrupting neurone function. The virus effectively suppresses immune responses, making it nearly impossible to treat once symptoms appear, leading to almost 100% fatality. Beyond its biological impact, rabies has influenced cultural stories like those of vampires and zombies, with its symptoms—such as aggression, fear of water, and neurological decay—providing eerie parallels to these myths. Despite modern medical advances, rabies remains one of the most feared infectious diseases due to its fatal nature. Written by Baraytuk Aydin Related articles: Rare zoonotic diseases / rAAV gene therapy REFERENCES CUSABIO (2020) Rabies virus overview: Structure, transmission, pathogenesis, symptoms, etc, CUSABIO. Available at: https://www.cusabio.com/infectious-diseases/rabies-virus.html (Accessed: 12 September 2024). Hendricks, A.G. et al. (2012) Dynein tethers and stabilizes dynamic microtubule plus ends, Current biology : CB. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347920/ (Accessed: 13 September 2024). Lahaye, X. et al. (2009) Functional Characterization of Negri Bodies (NBS) in rabies virus-infected cells: Evidence that NBS are sites of viral transcription and replication, Journal of virology. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715764/ (Accessed: 13 September 2024). Tarantola, A. (2017) Four thousand years of concepts relating to rabies in animals and humans, its prevention and its cure , MDPI . Available at: https://www.mdpi.com/2414-6366/2/2/5 (Accessed: 15 September 2024). Project Gallery

A rare neurological disease that is caused by a flaw in genetics Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Pseudo-Angelman Syndrome 03/04/26, 16:13 Last updated: Published: 07/09/24, 20:20 A rare neurological disease that is caused by a flaw in genetics This is article no. 8 in a series on Rare Diseases. Next article: Breaking down Tay-Sachs . Previous article: Apocrine carcinoma . An overview Name of the disease: Pseudo-Angelman Syndrome Other names the disease is known by: MBD5-Associated Neurodevelopmental Disorder (MAND) 2q23.1 microdeletion syndrome Del(2)(q23.1) monosomy 2q23.1 Prevalence rate in the US: <1000 Average life expectancy: mid-50s – early 70s for severe to moderate intellectual disabilities Mortality rate: <10% in individuals with severe to moderate intellectual disabilities (this rate is more than double the general population) Pseudo-Angelman syndrome is a neurological disease, which is classified as Rare since it affects fewer than 1000 people in the US (as reported by the National Institute of Health). However, the information on this disease, like other rare diseases, is incomplete. This article aims to raise awareness of rare neurological diseases such as Pseudo-Angelman syndrome. Onset of symptoms: the symptoms of the disorder can appear early as a newborn and an infant Its symptoms include: - Seizures - Moderate-severe learning difficulties- mental retardation (MR)- and behaviour issues (the roles of the frontal and parietal lobes in the brain are planning and executing actions, as well as proprioception) - Speech and developmental delays (one of the functions the temporal lobe in the brain is responsible for is audio processing and speech) - Trouble sleeping - Repetitive movements of the fingers, wrists, etc. or motor stereotypy Hypotonia, slow weight gain, and shorter height may also be present in children affected by the disease. Symptoms help diagnose the diagnosis, but only genetic testing confirms it. The genetic mechanism of the disease Genetic cause of the disease: a microdeletion on 2q23.1 A chromosomal deletion occurs when a region of a chromosome is removed, resulting in the loss of genetic material within that specific segment. A microdeletion affects an even smaller part on the chromosome. Hence, in Pseudo-Angelman syndrome, the 2q23.1 microdeletion involves the loss of a small section of DNA on chromosome no. 2. More specifically, the DNA is lost from position 23.1 on chromosome 2. The exact role of chromosome 2 is not yet known (there is active research in this field), but chromosome 2 likely contains protein-coding genes. The chances are that key proteins that genes in chromosome 2 code for, are not made when there is a 2q23.1 microdeletion i.e. the microdeletion removes these crucial genes, and so cells cannot produce the proteins. Thus, giving rise to Pseudo-Angelman syndrome in the individual. Indeed, research has shown that usually the MBD5 gene is deleted in patients with the syndrome (in one study, all 15 patients had lost this gene from the removed region). The next prominent gene that is deleted is EPC2 , which is a gene that is thought to be involved in causing MR. Inheritance of the disease: mostly de novo A study by van Bon et. al (2009) depicted that 10 out of 11 patients were shown to have de novo inheritance of 2q23.1 microdeletion. Comparison to Angelman syndrome See Table 1 The syndrome is called Pseudo-Angelman, so where does the Angelman part of the name come from? (The disease is named after Dr. Harry Angelman, who had first described and reported the syndrome in 1965). Angelman syndrome (AS) is also a rare disease, however, it has a higher prevalence rate than Pseudo-Angelman. One possibility could be in the way these different conditions come about in the first place. Loss of function (rather than a deletion) of the UBE3A gene in chromosome 15 from the mother, gives rise to AS. It is an example of an imprinting disorder. (Two copies of each chromosome are normally inherited, but in genomic imprinting, only one copy of a particular chromosome is passed on i.e. either the copy from the mother is inherited, or from the father- not both. Deletion, loss of function etc. may cause the other copy to not be inherited. Imprinting disorders lead to developmental and growth problems in the affected individual). In contrast, Pseudo-Angelman syndrome is often de novo, and not inherited. It is not an imprinting disorder like Angelman’s, because Pseudo-Angelman is caused by a microdeletion in 2q23.1. However, AS presents severe physical, learning, and intellectual problems. The syndrome causes seizures and developmental delays. The similarity in patients with Pseudo-Angelman can be seen here; therefore, it may be why Pseudo-Angelman is named so. Table 1: a comparison of AS and Pseudo-Angelman syndrome Angelman syndrome (AS) Pseudo-Angelman Syndrome Prevalence rate 1 in 20,000- 12,000 <1000 in the US Symptoms in common severe physical, learning, and intellectual problems seizures and developmental delays severe physical, learning, and intellectual problems seizures and developmental delays Cause Loss of function of UBE3A gene Microdeletion (of MBD5 and ECP2 genes among others) Chromosome affected Chromosome 15 Chromosome 2 (2q23.1) Mode of inheritance Genomic imprinting; inherited in an autosomal dominant way in rare cases De novo Are there any treatments for Pseudo-Angelman syndrome? Cure available: none There is no one cure to help patients with the disease, but depending on symptoms, treatment may be offered accordingly. Current treatments based on symptoms: - Seizures--> anti-seizure medicines - Behaviour issues--> behaviour therapy - Speech and developmental delays--> speech therapy - Difficulty sleeping--> medicine, sleep training Potential future treatments or cures: targeted therapy in chromosome 2 Latest research has confirmed Mbd5 as the primary driver of symptoms through the use of Mbd5 gene-trap mouse models, which mimic human behavioral and cognitive deficits- thus giving this syndrome a new term, MBD5-Associated Neurodevelopmental Disorder (MAND). The outlook for research into this disease Aside from discerning the exact roles and functions of the genes on chromosome 2, there is active research in targeted therapy for Pseudo-Angelman syndrome. Likely, once the rest of the roles of the genes on chromosome 2 are elucidated, efforts can be invested towards modifying or even inserting these genes (i.e. MBD5 ) back into the chromosome, which would lead to better protein expression. This could be a possible treatment for the rare neurological disease. Outside the molecular and genetic front, there should be increased awareness about this disease: this helps in reporting and diagnosing the syndrome, in addition to providing care and treatment to patients and their families. Summary In conclusion, Pseudo-Angelman Syndrome (now known as MBD5-Associated Neurodevelopmental Disorder (MAND)), is a rare 2q23.1 microdeletion syndrome, which gets its name from the imprinting disorder AS. Pseudo-Angelman is characterised by seizures, moderate to severe learning difficulties, and developmental delays. Hence, making it a neurological disease as well. Treatments are available according to symptoms; but efforts are ongoing to ascertain the roles of other chromosome 2 genes, especially Mbd5, leading to potential targeted therapy. -- Patient organisations specifically for this disease: - Chromsome Disorder Outreach - Unique The information in this article does not substitute professional medical advice. For any concerns, please refer to your doctor or local genetic centre. -- Written by Manisha Halkhoree Related article: Childhood intelligence REFERENCES van Bon, B., Koolen, D., Brueton, L. et al. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype. Eur J Hum Genet 18, 163–170 (2010). https://doi.org/10.1038/ejhg.2009.152 Mayo Clinic, 2024. Angelman syndrome . Retrieved from Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/angelman syndrome/diagnosis-treatment/drc-20355627#:~:text=Depending%20on%20your%20child's%20symptoms,sign%20language%20and%20picture%20communication. Medline Plus, 2024. Angelman syndrome . Retrieved from Medline Plus Gov: https://medlineplus.gov/genetics/condition/angelman-syndrome/#:~:text=Angelman%20syndrome%20affects%20an%20estimated%201%20in%2012%2C000%20to%2020%2C000%20people . National Institute of Health, 2024. 2q23.1 microdeletion syndrome . Retrieved from National Institute of Health: https://rarediseases.info.nih.gov/diseases/10998/2q231-microdeletion-syndrome Project Gallery

Comparative oncology Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link What can our canine friends tell us about cancer? 14/07/25, 15:12 Last updated: Published: 02/07/24, 10:04 Comparative oncology Comparative oncology is a field of study within cancer that has been adopted to study cancer and develop new therapies. It involves studying cancer in animals to uncover similarities between human and animal cancers. By combining scientific findings across a range of species, including companion animals such as dogs and horses or non-human primates such as monkeys, comparative oncology will advance cancer research and help develop effective novel therapies. This approach not only explores cancers in both animals and humans but also aims to bridge the gap between human and veterinary medicine. By examining similarities and differences in cancer biology, progression and treatment responses across species, comparative oncology provides valuable insights that can benefit both fields. Understanding how cancer behaves in animals can offer new perspectives and potential therapies for human patients. Conversely, while findings in human oncology can inform veterinary medicine, leading to improved diagnostics and treatments for animals. ( Figure 1 summarises the aims of comparative oncology). This article aims to explore this field of oncology further by discussing what it entails, the methodologies utilised, some recent advancements, and finally, things to look out for in the future. Comparative oncology has been developed and expanded into two areas of study. This includes spontaneous oncology and experimental oncology. Spontaneous oncology focuses on naturally occurring tumours in animals by investigating aspects of carcinogenesis, epidemiology, diagnosis, and treatment. It provides unique insights by drawing comparisons with human oncology research. These results can then be extrapolated to human oncology to gain a better understanding of cancer. This is because the similarities and differences observed in naturally occurring tumours across species provide valuable insights into underlying mechanisms within tumours and treatment responses. Experimental oncology serves as a distinct discipline where there are specialisations such as studying viral, chemical, and radiation oncogenesis alongside studying environmental factors such as pollution residues and food additives. This area involves studying both spontaneous tumours in animals and lab settings, where controlled conditions are used to explore different parts of cancer biology and treatment strategies. Additionally, the primary methodology utilised in comparative oncology involves studying spontaneous tumours in animals. Unlike artificially induced tumours in lab animals, these spontaneous tumours in pets closely mimic the complexity and heterogeneity of human cancers. For example, canines will live in similar living environments and experience similar external stimuli to their owner, such as pollution. The nature of these external stimuli means that they develop cancer in similar ways caused by epigenetic alterations, metabolic, and immune changes. (Figure 2 illustrates this process). Furthermore, comparative oncology uses advanced imaging techniques, genetic analysis, and immunological studies to predict pathways that may be shared among animals and humans which, could drive cancer development. Overall, these methods will allow the identification of promising therapies which directly target cancer and expand on current treatment choices such as chemotherapy and immunotherapy. One of the recent advancements in comparative oncology relates to osteosarcomas. This refers to cancer cells which begin to grow in the bones. For this specific form of cancer, molecular signatures were identified to predict clinical outcomes for both humans and canines, which can help improve treatment outcomes. Led by Amy K. LeBlanc, scientists have identified gene activity patterns in osteosarcoma tumours in nearly 200 dogs, revealing distinct groups with varying prognoses. These findings help us understand the biology behind osteosarcomas further and can potentially help us develop targeted therapies that take advantage of the immune system to treat the disease in both species. This potentially includes a range of therapies including PD-L1 inhibitors and cancer vaccines targeting the immune system. Moreover, breakthroughs in immunotherapies such as checkpoint inhibitors and CAR-T cell therapy are effective in treating haematological malignancies in both humans and canines. Furthermore, studies in canine melanoma reveal similar gene expression changes to human melanoma, such as in the PI3K/AKT/mTOR and MAPK pathways, even when the driver mutations are different. (Figure 3 shows how the pathway contributes to cancer). Useful data was provided in trials using companion animals with spontaneous tumours, providing an insight into safety, dosage, and efficacy, which have paved the way to develop treatments for both species. To conclude, it is clear with comparative oncology, researchers will be able to identify new molecular targets, assess novel drugs, and identify patient populations which will benefit the most from these therapies. It holds great promise in helping streamline cancer diagnosis further and even plays a role in preventing cancer. While the field shows great potential, more studies still need to be conducted to understand the similarities and differences in cancers between animals and humans. Additionally, more collaboration is needed amongst oncologists, veterinarians, and researchers across these disciplines to harness collective expertise to address questions relating to cancer diagnosis, treatment, and prevention. Ultimately, this field will help us identify new avenues of treating and diagnosing cancer whilst improving healthcare outcomes for humans and animals alike. Written by Harene Elayathamby Related articles: Why blue whales don't get cancer / Rare zoonotic diseases REFERENCES Schiffman, J.D. and Breen, M. (2015) ‘Comparative oncology: What dogs and other species can teach us about humans with cancer’, Philosophical Transactions of the Royal Society B: Biological Sciences , 370(1673), p. 20140231. doi:10.1098/rstb.2014.0231. Oh, J.H. and Cho, J.-Y. (2023) ‘Comparative oncology: Overcoming human cancer through companion animal studies’, Experimental & Molecular Medicine , 55(4), pp. 725–734. doi:10.1038/s12276-023-00977-3. Al, B. and C., C. (2007) ‘Chapter 1 COMPARATIVE ONCOLOGY ’, in Comparative oncology . Bucharest (RO): The Publishing House of the Romanian Academy, p. 1. Vail, D.M., LeBlanc, A.K. and Jeraj, R. (2020) ‘Advanced cancer imaging applied in the comparative setting’, Frontiers in Oncology , 10. doi:10.3389/fonc.2020.00084. New findings highlight shared features of human and canine osteosarcoma (2023) Center for Cancer Research . Available at: https://ccr.cancer.gov/news/article/new-findings-highlight-shared-features-of-human-and-canine-osteosarcoma (Accessed: 02 March 2024). Mochel, J.P. et al. (2018) Car T-cell immunotherapy in human and veterinary oncology: Changing the odds against hematological malignancies [Preprint]. doi:10.20944/preprints201811.0525.v1. LeBlanc AK, Mazcko CN, Khanna C. (2016) ‘Defining the Value of a Comparative Approach to Cancer Drug Development’, Clinical cancer research : an official journal of the American Association for Cancer Research , 22(9). p. 2133-2138. doi: 10.1158/1078-0432.CCR-15-2347 FIGURE REFERENCES Boddy, A.M., Harrison, T.M. and Abegglen, L.M. (2020) ‘Comparative oncology: New insights into an ancient disease’, iScience , 23(8), p. 101373. doi:10.1016/j.isci.2020.101373. Oh, J.H. and Cho, J.-Y. (2023) ‘Comparative oncology: Overcoming human cancer through companion animal studies’, Experimental & Molecular Medicine , 55(4), pp. 725–734. doi:10.1038/s12276-023-00977-3. Rascio, F. et al. (2021) ‘The pathogenic role of PI3K/Akt pathway in cancer onset and drug resistance: An updated review’, Cancers , 13(16), p. 3949. doi:10.3390/cancers13163949. Project Gallery