Looking at p53 mutations and cancer predisposition Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Decoding p53: the guardian against cancer 09/07/25, 15:03 Last updated: Published: 23/11/23, 11:38 Looking at p53 mutations and cancer predisposition Being a tumour suppressor protein, p53 encoded by the TP53 gene plays a critical role in regulating cell division and preventing the formation of tumours. Its function in maintaining genome stability is vital in inhibiting cancer development. Understanding p53 Located on chromosome locus 17p13.1, TP53 encodes the p53 transcription factor 1. Consisting of three domains, p53 can directly initiate or suppress the expression of 3661 different genes involved in cell cycle control and DNA repair 2. With this control, p53 can influence cell division on a massive scale. Cancer is characterised by uncontrolled cell division, which can occur due to accumulated mutations in either proto-oncogenes or tumour suppressor genes. Wild-type p53 can repair mutations in oncogenes such that they will not affect cell division. However, if p53 itself is mutated, then its ability to repair DNA and control the cell cycle is inhibited, leading to the emergence of cancer. Mutations in TP53 are actually the most prevalent genetic alterations found in patients with cancer. The mechanisms by which mutated p53 leads to cancer are manifold. One such mechanism is p53’s interaction with p21. Encoded by CDKN1A , p21 is activated by p53 and prevents cell cycle progression by inhibiting the activity of cyclin-dependent kinases (CDKs). Therefore, we can see that a non-functional p53 would lead directly to uncontrolled cell division and cancer. Clinical significance The importance of p53 in preventing cancer is highlighted by the fact that individuals with inherited TP53 mutations (a condition known as Li-Fraumeni syndrome or LFS) have a significantly greater risk of developing any cancer. These individuals inherit one defective TP53 allele from one parent, making them highly susceptible to losing the remaining functional TP53 allele, ultimately leading to cancer. Loss of p53 also endows cells with the ability to ignore pro-apoptotic signals such that if a cell becomes cancerous, it is far less likely to undergo programmed cell death 3. Its interactions with the apoptosis-inducing proteins Bax and Bak, are lost when mutated, thus leading to cellular apoptosis resistance. The R337H mutation in TP53 is an example of the founder effect at work. The founder effect refers to the loss of genetic variation when a large population descends from a smaller population of fewer individuals. The descendants of the initial population are much more likely to harbour genetic variations that are less common in the species as a whole. In southern Brazil, the R337H mutation in p53 is present at an unusually high frequency 4 and is thought to have been introduced by European settlers several hundred years ago. It is responsible for a widespread incidence of early-onset breast cancers, LFS, and paediatric adrenocortical tumours. Interestingly, individuals with this mutation can trace their lineage back to the group of European settlers that set foot in Brazil hundreds of years ago. Studying p53 has enabled us to unveil its intricate web of interactions with other proteins and molecules within the cell and unlock the secrets of cancer development and potential therapeutic strategies. By restoring or mimicking the functions of p53, we may be able to provide cancer patients with some relief from this life-changing condition. Written by Malintha Hewa Batage Related articles: Zinc finger proteins / Anti-freeze proteins Project Gallery

Beavers alter their landscape through dams, canals, and felling trees Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Beavers are back in Britain, ‘wood’ you like to know why? 08/03/26, 18:09 Last updated: Published: 03/12/24, 12:05 Beavers alter their landscape through dams, canals, and felling trees This is article no. 3 in a series on animal conservation. Next article: Pangolins: from poached to protected . Previous article: Conserving the California condor Eurasian beavers ( Castor fiber ) transform freshwater habitats so dramatically that they are nicknamed ‘ecosystem engineers’. Their dam-building and tree-felling activities could reduce flood risk and increase biodiversity. After being hunted to extinction centuries ago, beavers have been reintroduced to Britain in both organised and illicit ways. This article will describe where they have been reintroduced in Britain, and the impact they could have. Ecological importance of beavers By building dams, Eurasian beavers alter their habitat - often for the better. Beaver dams are made from wood, stones, and mud. They control the flow of river water, reducing the risk of floods and droughts. The resulting slower water is a good place for amphibians to lay eggs and undergo the aquatic part of their life cycle. As water builds up behind the dam, it converts the area into a wetland - a source of drinking water for animals like bats and an excellent carbon sink. Meanwhile, invertebrates can lay eggs or hide from predators in the spaces within beaver dams ( Figure 1 ). Further up the food chain, beaver dams have complex effects on fish. Although the still water provides habitat for overwintering and rearing young, dams restrict the movement of fish species like salmon. However, most studies have concluded that beaver dams benefit freshwater biodiversity. Dams are not the only way Eurasian beavers improve their landscape. To access food and construction materials easily, beavers dig canals – which make the habitat better drained and more complex. Moreover, beavers gnaw at tree trunks and branches, sometimes knocking over entire trees. This creates deadwood where terrestrial invertebrates can live. Felling trees also allow sunlight to reach the river surface, promoting aquatic plant growth. When beavers gnaw at willow trees, they create propagules, which disperse along the beaver-made canal network and grow downstream. These new willow trees stabilise the river bank and further reduce the flood risk. Humans often trim back trees to stimulate their growth – called coppicing – but beavers do this free of charge. Coppicing, dam building, and canal digging are just a few ways beavers save the human costs of restoring and protecting natural habitats. Extinction and reintroduction However, Eurasian beavers used to be more exploited than appreciated. They were hunted for their fur, meat, and a secretion called castoreum, which is used in perfume and pharmaceuticals. Exactly when and how the beaver population went extinct from Britain is unclear, but the last written record of a beaver is from 1526 in Scotland and 1780 in England. Since then, the British turned wetlands into farmland and forgot about beavers … until recently. After centuries, beavers returned to Scotland in the late 2000s. A handful of beavers were spotted in River Tay about 15 years ago, after either an enclosure escape or an illegal release. There are 114 families in this illegal population, which has genetic origins in Germany. The first official beaver reintroduction occurred in Knapdale Forest, Scotland, in 2009 – but this population did not grow as quickly as the River Tay one. With scepticism, the reintroduction of Eurasian beavers to Scotland was deemed a success, and they became a ‘European Protected Species’ in Scotland in 2019. Seeing Eurasian beavers thriving in Scotland encouraged reintroduction plans in England. In the English county of Devon, River Otter showed signs of beaver presence since 2008 and breeding since 2013. Authorities were worried these illegally released beavers would spread foreign diseases to local wildlife, but the public campaigned to let the beavers be. Public affection for beavers led to the River Otter Beaver Trial in 2015, where two breeding pairs were released into the river after thorough health checks. By 2019, the number of breeding pairs grew to seven ( Figure 2 ). Therefore, beavers have successfully returned to England. Encouraged by the unofficial projects, in February 2025 the UK government announced a new programme to officially re-introduce beavers to England. This programme ensures existing beaver populations are carefully managed and new reintroductions are licensed. Since then, beavers have been legally released in Dorset (March 2025) and Cornwall (February 2026). Thus, the UK government has joined the British public in returning Eurasian beavers to their ancestral home. Conclusion Beavers alter their landscape through dams, canals, and felling trees. However, in Britain, they were hunted to extinction a long time ago. Although beavers first returned to England and Scotland illegally, they now live in healthy, growing populations supported by the government . Hopefully they will remain protected and loved by the public, helping us to restore wetlands and improve British freshwater biodiversity. Written by Simran Patel Related article: Vicuna conservation REFERENCES Andersen, L.H. et al. (2023) ‘Can reintroduction of beavers improve insect biodiversity?’, Journal of Environmental Management , 337, p. 117719. Available at: https://doi.org/10.1016/j.jenvman.2023.117719 . Brazier, R.E., Elliott, M., Andison, E., Auster, R.E., Bridgewater, S., Burgess, P., Chant, J., Graham, H., Knott, E., Puttock, A.K., Sansum, P., Vowles, A., (2020) ‘River Otter Beaver Trial: Science and Evidence Report’. Brazier, R.E. et al. (2021) ‘Beaver: Nature’s ecosystem engineers’, WIREs Water , 8(1), p. e1494. Available at: https://doi.org/10.1002/wat2.1494 . Campbell-Palmer, R. et al. (2020) ‘Beaver genetic surveillance in Britain’, Global Ecology and Conservation , 24, p. e01275. Available at: https://doi.org/10.1016/j.gecco.2020.e01275 . Department for Environment, Food & Rural Affairs and Natural England (2025) Wild beavers: Nature’s engineers to return to English waterways , GOV.UK . Available at: https://www.gov.uk/government/news/wild-beavers-natures-engineers-to-return-to-english-waterways (Accessed: 7 March 2026). Gaywood, M., Batty, D. and Galbraith, C. (2008) ‘Reintroducing the European Beaver in Britain’, British Wildlife , 19, pp. 381–391. Halley, D.J., Saveljev, A.P. and Rosell, F. (2021) ‘Population and distribution of beavers Castor fiber and Castor canadensis in Eurasia’, Mammal Review , 51(1), pp. 1–24. Available at: https://doi.org/10.1111/mam.12216 . Harris, S. (2025) ‘Wild beavers make historic return to England at Dorset nature reserve’, BBC News , 5 March. Available at: https://www.bbc.co.uk/news/articles/cwygxvzpkevo (Accessed: 7 March 2026). Hooker, J. et al. (2024) ‘Re-establishing historic ecosystem links through targeted species reintroduction: Beaver-mediated wetlands support increased bat activity’, Science of The Total Environment , 951, p. 175661. Available at: https://doi.org/10.1016/j.scitotenv.2024.175661 . Robinson, C. (2026) Two pairs of beavers released in Cornwall by wildlife trust , BBC News . Available at: https://www.bbc.co.uk/news/articles/cm2x9ndl4l9o (Accessed: 7 March 2026). Wilson, J.B., Bradley, J. and Bremner-Harrison, S. (2024) ‘The short-term impact of Eurasian beavers ( Castor fiber ) post-reintroduction on amphibian abundance and diversity in a lentic environment’, The Glasgow Naturalist , 28(2). Available at: https://doi.org/10.37208/tgn28224 . Project Gallery

Laser Interferometric Gravitational-wave Observatory (LIGO) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The physics of the world’s largest gravitational-wave observatory: LIGO 23/10/25, 11:23 Last updated: Published: 11/05/24, 12:16 Laser Interferometric Gravitational-wave Observatory (LIGO) Since the confirmation of detection, talk of gravitational waves has drastically increased in the public forum. In February 2016, the Laser Interferometric Gravitational-wave Observatory (LIGO) Collaboration announced that they had sensed gravitational waves, or ripples in spacetime, caused by the collision of two black holes approximately 1.3 billion light years away. Such an amazing feat quickly became globalized news with many asking how it could be physically possible to detect an event occurring at an unimaginable distance? For some, the entire situation feels incomprehensible. Although named an observatory, LIGO looks quite different from observatories such as the late Arecibo Observatory in Puerto Rico, the Very Large Array (VLA) in New Mexico, or the Lowell Observatory in Arizona. Instead of being related to the traditional telescope concept, LIGO is comprised of two interferometers, one in Hanford, Washington and the other in Livingston, Louisiana, that use lasers to detect vibrations in the fabric of spacetime. An interferometer is an L-shaped apparatus with mirrors at the end of each arm specifically positioned to split the incoming light waves, specifically in this case laser waves, into an interference pattern. This pattern is then detected by a device called a photodetector, which converts the pattern into carefully recorded data. When an incredibly violent event occurs, two black holes colliding, for instance, that action results in a massive release of energy that ripples across the fabric of spacetime. The energy from the event vibrates the laser light causing a change in the recorded light pattern. This change is also recorded by the photodetector and stored as data, which scientists can collect to analyze as needed. Because the LIGO detector is so sensitive, there are a number of systems in place to maintain its functionality and reliability. The apparatus is comprised of four main systems: 1) seismic isolation that focuses on removing non-gravitational-wave detections (also called ‘noise’) 2) optics that regulate the laser 3) a vacuum system preserving the continuity of the laser by removing dust from the components 4) computing infrastructure that manages the collected scientific data. The collaboration of these systems helps to minimize the number of false detections. False detections are also kept at a minimum with the effective communication between the Washington and Louisiana LIGO sites. It took months for the official announcement of the 2015 gravitational-wave detection because both locations had to compare data to ensure that the detection of one apparatus was also accurately detected by the other apparatus. Because of human activity on Earth, there can be a number of vibrations similar to gravitational-wave ripples, but ultimately are shown to be terrestrial events rather than celestial ones. So, while LIGO physics itself is fairly straightforward, the interpretation of the gathered data tends to be tricky. Written by Amber Elinsky Related articles: the DESI instrument / the JWST / The physics behind cumulus clouds / Light Project Gallery

AI in developing different space technologies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Artificial intelligence in space 11/04/26, 15:03 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

What my role entails Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring My Role as a Clinical Computer Scientist in the NHS 17/04/25, 11:23 Last updated: Published: 06/05/24, 14:03 What my role entails When we think about career choices, we’re often presented with singular choices. Clinical Scientific Computing is a field that combines healthcare and computing. Despite it being relatively unknown, it is an important cog in the healthcare machine. When I applied for the Scientific Training Program in 2021, the specialism I applied for (Clinical Scientific Computing) had one of the lowest application rates out of approximately 27 specialisms. Awareness of this area has now improved, both thanks to better advertisement and exponential advancements in technology and healthcare. According to the NHS, there are now 26.8 thousand full-time equivalent healthcare scientists in England's NHS. As a clinical computer scientist, one's expertise can be applied in diverse settings, including medical physics laboratories and clinical engineering departments. My role in radiotherapy involves overseeing the technical aspects of clinical workflows, ensuring the seamless integration of technology in patient care. Training is a crucial part of being a proficient computer scientist. Especially with the growth of scientific fields in the NHS, there's always an influx of juniors and trainees, and that in turn, warrants the need for excellent trainers. A clinical scientist is someone who is proficient in their craft and able to explain complex concepts in layman's terms. As Einstein famously said: If you can't explain it to a 6-year-old, you can't understand it yourself. Although I am still technically a trainee, I am expected to partake in the training of the more junior trainees in my schedule. On a typical day, this may be as simple as explaining a program and demonstrating its application, or I may dismantle a PC and go through each component, one by one. At the core of clinical science is research. You won't go a day without working on at least one project and sometimes these may not even be your own. Collaboration with others is a huge part of the job. Every scientist has a different way of thinking about a problem, and this is exactly what keeps the wheels spinning in a scientific department. There are numerous times when I seek the help of others and vice versa. It is difficult to talk about 'typical' projects because they are often so varied in scientific computing, but it is likely that you will find yourself working on a variety of programming tasks. Having clinical know-how is crucial when working on projects in this field, and that aspect is exactly what separates the average computer scientist from the clinical computer scientist. A project I am currently working on involves radiation dose calculations, which naturally involves understanding the biological effects of radiation on the human body. This isn't a typical software development project so having a passion for healthcare is absolutely necessary. The unpredictability of technology means that troubleshooting is a constant aspect of our work. If something goes wrong in the department (which it often does), it is our responsibility as technical experts to quickly but effectively diagnose and fix the problems. The clinical workflow is highly sensitive in healthcare especially the cancer pathway where every minute counts. If a radiographer is unable to access patient records or there is an error with a planning system, this can have detrimental effects on the quality of patient care. Addressing errors, like those in treatment planning systems, necessitates a meticulous approach to diagnosis, often leading us from error code troubleshooting to on-site interventions. For example, I may be required to physically attend a treatment planning room and resolve an issue with the PC. This narrative offers a glimpse into the day-to-day life of a clinical computer scientist in the NHS, highlighting the critical blend of technical skill, continuous learning, and the profound impact on patient care. Through this lens, we can hopefully appreciate the essential role of clinical scientific computing in advancing healthcare, marked by innovation, collaboration, and a commitment to improving patient outcomes. This narrative offers a glimpse into the day-to-day life of a clinical computer scientist in the NHS, highlighting the critical blend of technical skill, continuous learning, and the profound impact on patient care. Through this lens, we can hopefully appreciate the essential role of clinical scientific computing in advancing healthcare, marked by innovation, collaboration, and a commitment to improving patient outcomes. For more information on this specialism . Written by Jaspreet Mann Related articles: Virtual reality in healthcare / Imposter syndrome in STEM Project Gallery

Unmasking the complexities of the condition Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Crohn's disease 09/07/25, 15:01 Last updated: Published: 22/03/24, 20:16 Unmasking the complexities of the condition Introduction Crohn's disease is a chronic inflammatory condition that primarily targets the gastrointestinal tract. While it commonly afflicts individuals aged 20 to 50, it can also manifest in children and older adults, albeit less frequently. Symptoms of Crohn's disease vary widely and may include skin lesions spanning from the mouth to the anus, along with prevalent issues such as diarrhoea, abdominal pain, weight loss, rectal bleeding, fatigue, and fever. Diagnosis Diagnosing Crohn's disease can be challenging due to its similarity to other conditions. However, specific symptoms like bloody diarrhoea, iron deficiency, and unexplained weight loss are significant indicators that warrant further investigation by a gastroenterologist. Many tests that can confirm Crohn’s disease: Endoscopy: endoscopy, including procedures like colonoscopy and upper endoscopy, is a dependable method for diagnosing Crohn's disease and distinguishing it from other conditions with similar symptoms. During an endoscopy, a thin tube called an endoscope is inserted into the rectum to visually inspect the entire gastrointestinal tract and collect small tissue samples for further analysis. Imaging: Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography are valuable tools for assessing disease activity and detecting complications associated with Crohn's disease. These imaging techniques can examine areas of the gastrointestinal tract that may not be accessible via endoscopy, providing comprehensive insights into the condition's progression and associated issues. Laboratory testing: various laboratory tests, including complete blood count, C-reactive protein levels, pregnancy tests, and stool samples, are conducted to screen for Crohn's disease. These tests are typically the initial step in diagnosis, helping to avoid the necessity for more invasive procedures like endoscopies and imaging. Additionally, laboratory testing may involve assessing inflammatory markers such as erythrocyte sedimentation rate (ESR) and faecal calprotectin to further aid in diagnosis and monitoring of the condition. Treatment and prevention While there is currently no cure for Crohn’s disease, numerous treatments have been developed over time to effectively manage symptoms and sometimes even induce remission. When determining a treatment plan for patients, factors such as age, specific symptoms, and the severity of inflammation are taken into careful consideration. Corticosteroids and immunomodulators are medications commonly used to manage Crohn’s disease. Corticosteroids work by reducing inflammation and suppressing the immune system, typically employed to address flare-ups due to their rapid action. However, they are not suitable for long-term use as they may lead to significant side effects. In contrast, maintenance therapy often involves immunomodulators such as azathioprine, methotrexate, or biologic agents like anti-TNF drugs (such as infliximab or adalimumab). These medications target specific immune pathways to enhance the effectiveness of the immune system. Research indicates that immunomodulators are associated with fewer adverse effects compared to corticosteroids and are effective in maintaining remission. Monoclonal antibody treatment is another approach used to manage symptoms and sustain remission in Crohn's disease. These therapies are categorised as biologic treatments, targeting precise molecules involved in inflammation and the immune response. Despite carrying certain risks, such as infections, the likelihood of developing cancer with these treatments is typically deemed low. Crohn’s disease frequently leads to complications that may necessitate surgical intervention. Gastrointestinal surgeries can greatly alleviate symptoms and enhance the quality of life for patients. However, surgery is usually considered only when medical therapy proves insufficient in controlling the disease or when complications arise. Although the exact cause of Crohn’s disease remains uncertain, factors such as genetics, immune system dysfunction, and environmental influences are believed to contribute to its development. While there is no definitive evidence pinpointing specific causative factors, numerous studies suggest potential links to an unhealthy diet and lifestyle, dysbiosis (imbalance of healthy and unhealthy gut bacteria), smoking, and a family history of the disease. Therefore, it is crucial to minimise exposure to these risk factors in order to decrease the likelihood of developing Crohn’s disease. Written by Sherine Abdul Latheef Related articles: the gut microbiome / the dopamine connection / Diverticular disease / Mesenchymal stem cells REFERENCES Veauthier B, Hornecker JR. Crohn's Disease: Diagnosis and Management. Am Fam Physician. 2018;98(11):661-669. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017;389(10080):1741-1755. doi:10.1016/S0140-6736(16)31711-1 Mills SC, von Roon AC, Tekkis PP, Orchard TR. Crohn's disease. BMJ Clin Evid. 2011;2011:0416. Published 2011 Apr 27. Sealife, A. (2024) Crohn’s disease, Parkland Natural Health. Available at: https://wellness-studio.co.uk/crohns-disease/ (Accessed: 09 March 2024). How to stop anxiety stomach pain & cramps (2022) Calm Clinic - Information about Anxiety, Stress and Panic. Available at: https://www.calmclinic.com/anxiety/symptoms/stomach-pain (Accessed: 09 March 2024). Project Gallery

The mechanisms of the disease Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Alzheimer's disease 25/03/26, 16:50 Last updated: Published: 21/07/23, 10:36 The mechanisms of the disease Introduction to Alzheimer’s disease Alzheimer’s disease is a neurodegenerative disease that results in cognitive decline and dementia with increasing age, environmental and genetic factors contributing to its onset. Scientists believe this is the result of protein biomarkers that build-up in the brain and accumulate within neurones. As of 2020, 55 million people suffer with dementia, with Alzheimer’s being a leading cause. Thus, it is crucial we develop efficacious treatments, with final adverse effects. Some disease-modifying therapies, such as lecanemab and donanemab, were approved for early-stage use but are not currently funded by the NHS due to cost-effectiveness, making them accessible only via private healthcare. The disease is most common in people over 65, with 1/14 affected in the UK, thus, there is a huge emphasis on defining the disorder and developing drug treatments. The condition results in difficulty with memory, planning, decision making and can result in co-morbidities such as depression or personality change. This short article will explain the pathology of the disorder and the genetic predispositions for its onset. It will also explore future avenues for treatment, such as the drug I ecanemab that may provide, “a new era for Alzheimer’s disease”. Pathology and molecular aspects The neurodegeneration seen in Alzheimer’s has, as far, been associated protein dispositions in the brain, such as the amyloid precursor protein (APP) and Tau tangles. This has been deduced by PET scans and post-mortem study. APP, located on chromosome 21, is responsible for synapse formation and signalling. It is cleaved to b-amyloid peptides by enzymes called secretases, but overexpression of both these factors can be neurotoxic (figure 1). The result is accumulation of protein aggregates called beta-amyloid plaques in neurons, impairing their survival. This deposition starts in the temporo-basal and front-medial areas of the brain and spreads to the neocortex and sensory-motor cortex. Thus, many pathways are affected, resulting in the characteristic cognitive decline. Tau proteins support nerve cells structurally and can be phosphorylated at various regions, changing the interactions they have with surrounding cellular components. Hyperphosphorylation of these proteins result in the Tau pathology in the form of tau oligomer (short peptides) that is toxic to neurons. These enter the limbic regions and neocortex. It is not clearly defined which protein aggregate proceeds the other, however, the amyloid cascade hypothesis suggests that b-amyloid plaque pathology comes first. It is speculated that b-amyloid accumulation leads to activation of the brain’s immune response, the microglial cells, which then promotes the hyperphosphorylation of Tau. Sometimes, there is a large release of pro-inflammatory cytokines, known as a cytokine storm, that promotes neuroinflammation. This is common amongst older individuals, due to a “worn-out” immune system, which may in part explain Alzheimer’s disease. Genetic component to Alzheimer’s disease There is strong evidence obtained through whole genome-sequencing studies (WGS), that suggests there is a genetic element to the disease. One gene is the Apoliprotein E (APOE) gene, responsible for b-amyloid clearance/metabolism. Some alleles of this gene show association with faulty clearance, leading to the characteristic b-amyloid build-up. In the body, proteins are made consistently depending on need, a dysregulation of the recycling process can be catastrophic for the cells involved. PSEN1 gene that codes for the presenilin 1 protein, part of a secretase enzyme complex. As mentioned, the secretase enzyme is responsible for the cleavage of APP, the precursor for b-amyloid. Variants of this gene have been associated with early onset Alzheimer’s disease, due to APP processing being altered to produce a longer form of the b-amyloid plaque. The genetic aspects to Alzheimer’s disease are not limited to these genes, and in actuality, one gene can have an assortment of mutation that results in a faulty protein. Understanding the genetic aspects, may provide avenue for gene therapy in the future. Treatment Understanding the point in which the “system goes wrong” is crucial for directing treatment. For example, we may use secretase inhibitors to reduce the rate of plaque formation. An example of this is the g- secretase BACE1 inhibitor. There is a need for this drug-type to be more selective to its target, as has been found to produce unwanted adverse effects. A more selective approach may be to target the patient’s immune system with the use of monoclonal antibodies (mAb). This means designing an antibody that recognises a specific component, such as the b-amyloid plaque, so it may bind and then encourage immune cells to target the plaque (figure 3). An example is Aducanumab mAb, which targets b-amyloid as fibrils and oligomers. The Emerge study demonstrated a decrease in amyloid by the end of the 78-week study. As of June 2021, Aducanumab received approval from the FDA for prescription of this drug, but this is controversial as there are claims it brings no clinical benefit to the patient. The future of Alzheimer’s disease Of note, drug development and approval is a slow process, and there must be a funding source in order to carry out plans. Thus, particularly in Alzheimer’s, it is relevant to educate the public and funding bodies to supply the financial support to the process. However, with many hits (potential drug candidates), these often fail at phase III clinical trials. Despite this, another mAb, lecanemab, has recently been approved by the FDA (2023), due to its ability to slow cognitive decline by 27% in early Alzheimer’s disease. The Clarity AD study on Iecanemab, found the drug benefited memory and thinking, but also allowed for better performance of daily tasks. This drug is currently being prescribed on a double-blind basis, meaning a patient may either receive the drug or the placebo. This study shows a hope for those suffering from the disease. Drugs that have targeted the Tau tangles, have as far, not been successful in clinical trials. However, the future of Alzheimer’s treatment may be in the combination therapy directed to both Tau protein and b-amyloid. Washington universities neurology department have launched a trial known as Tau NextGen, in which participants will receive both Iecanemab and tau-reducing antibody. Conclusion This article provides a summary to what we know about Alzheimer’s disease and the potential treatments of the future. Overall, the future of Alzheimer’s treatment lies in the combination therapy to target known biomarkers of the disease. Written by Holly Kitley Related articles: CRISPR-Cas9 as Alzheimer's treatment / Hallmarks of Alzheimer's / Sleep and memory loss 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, 17:13 Last updated: Published: 07/09/24, 21:20 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

Considering how non-covalent interactions can govern the way molecules recognise and organise themselves Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Chemistry Beyond the Molecule (Supramolecular Chemistry) Last updated: 06/09/26, 11:47 Published: 17/09/26, 08:00 Considering how non-covalent interactions can govern the way molecules recognise and organise themselves Introduction How many times have you performed a reaction and ignored the solvent? Or failed to consider the potential interactions between each reagent, or between the solvent and reagents? As chemists, we are often guilty of focusing on the molecules undergoing the reaction and treating everything else as background. Although this approach is intuitive, molecular behaviour is also influenced by interactions with surrounding molecules. To truly understand a system, we must therefore look ‘beyond the molecule’. Supramolecular chemistry, or ‘chemistry beyond the molecule’, was described by Jean- Marie Lehn as the ‘chemistry of the intermolecular bond’. Broadly, this means considering how non-covalent interactions can govern the way molecules recognise and organise themselves. Although these interactions are individually weaker than covalent bonds, their combined effects can have profound consequences, from stabilising the structures of proteins and DNA to directing the assembly of larger molecular systems. Choosing solvents Perhaps the most common synthetic application of supramolecular chemistry regards the selection of solvents. While frequently overlooked, selecting the correct solvent can have a direct impact on reaction kinetics and success, particularly with regards to SN1 and SN2 reactions. For example, let’s consider a simple SN1 reaction between 2-bromo-2-methylpropane and sodium chloride in water. Water is considered a polar protic solvent and is therefore well suited to facilitating an SN1 mechanism. Mechanistically, the first step involves the loss of the bromide leaving group to form a carbocation intermediate. Water facilitates this process through its intermolecular interactions with the charged species involved. As a polar protic solvent, water can act as a hydrogen bond donor and solvate the departing bromide ion. More importantly, water can stabilise the developing positive charge via ion-dipole interactions with the oxygen lone pairs orientated towards the carbocation. This stabilises the transition state, reducing the activation barrier of the rate determining step ( Figure 1 ). Note- competing reaction: Although water stabilises the carbocation intermediate and solvates the bromide leaving group, it is also a nucleophile. In an aqueous solution, water is present at a very high concentration and can directly trap the tert-butyl carbocation. Consequently, 2-bromo-2-methylpropane undergoes solvolysis, producing 2-methyl-2-propanol (tert-butanol). Chloride ions from NaCl can potentially compete as nucleophiles. Alternatively, SN2 reactions are known to be accelerated by polar aprotic solvents. This is not surprising when you consider the differences in reaction mechanism. Unlike protic solvents, aprotic solvents cannot act as hydrogen bond donors. Therefore, the nucleophile is less strongly solvated, accelerating the rate of nucleophilic attack ( Figure 2 ). Introducing crown ethers and cryptands In 1987, the Nobel Prize in chemistry was awarded to Cram, Pedersen and Lehn for their work on supramolecular chemistry. This section will focus on the development of crown ethers and cryptands by Pedersen and Lehn, respectively. A crown ether is a macrocyclic molecule containing multiple oxygen atoms within its ring. The arrangement of these atoms creates a specific sized cavity which can selectively bind alkali metal ions through ion-dipole interactions. The size and geometry of this cavity play an important role in determining which ions can be most effectively accommodated. For example, consider the molecule 18-crown-6, known for effectively binding potassium ions. The name 18-crown-6 refers to its 18-membered ring, of which 6 atoms are oxygen. Its cavity diameter of 2.60-3.20 Å matches the diameter of a potassium cation (2.66 Å) favouring strong binding. However, the strength of this interaction is also dependent on the surrounding solvent ( Figure 3 ). The selectivity of crown ethers can be demonstrated by comparing 18-crown-6 with 15- crown-5. The smaller cavity of 15-crown-5 is better suited to the smaller sodium ion, illustrating how subtle changes in molecular structure can influence which ions a molecule recognises and binds. Cryptands take this principle a step further. Like crown ethers, they can bind alkali metal ions, but their 3D macrocyclic structure creates a more enclosed cavity ( Figure 4 ). The 3D structure of the cryptand provides significant advantages over the crown ether. Its donor atoms are preorganised around the cavity, reducing the structural rearrangement required to bind the ion. Once bound, the metal ion is encapsulated within a cage, making dissociation more difficult. Synthetically, crown ethers and cryptands can exploit this strong binding to separate an alkali metal cation from its counterion. This is particularly useful for reactions involving bases. By selectively complexing the cation, the nucleophilicity of the base increases, improving its efficiency within a given reaction ( Figure 5 ). Mechanically interlocked molecules The power of supramolecular chemistry is often the ability to direct molecular self-assembly through several simultaneous intermolecular interactions. Synthetically, this has been exploited to create a range of interesting molecular structures and topologies, including catenanes and rotaxanes. A catenane is a mechanically interlocked molecule (MIM) formed when two or more macrocyclic rings become intertwined. The rings are described as interlocked because they cannot separate without breaking a covalent bond. The ring structures form selectively through favourable intermolecular interactions. One example is Stoddart’s synthesis of a catenane containing a cyclobis(paraquat-p- phenylene) ring, commonly known as the ‘blue box’. The electron-deficient bipyridinium units within the ‘blue box’ interact favourably with electron-rich aromatic groups in the second macrocycle. These favourable donor-acceptor interactions help orient each component before the final covalent bonds are formed ( Figure 6 ). Another example of a MIM is the rotaxane. Rather than two rings being interlocked, a rotaxane consists of a macrocyclic ring threaded onto a linear molecular ‘axle’. Bulky groups are used at the ends of the ‘axle’ to prevent the ring slipping off. Again, the macrocyclic ring can move along the ‘axle’, with its position determined by favourable intermolecular interactions ( Figure 7) . Conclusion Supramolecular chemistry broadens our understanding of how intermolecular interactions influence chemical behaviour, extending this perspective from the bulk properties of matter to the behaviour and organisation of individual molecules. From solvent selection to molecular topology, supramolecular chemistry is a powerful tool to understand reaction outcomes and design complex molecular structures. This article serves as an introduction to a broad field of active research, with exciting applications in dynamic combinatorial synthesis and molecular machinery. Written by Antony Lee Related article: Chemistry beyond carbon REFERENCES The Nobel Prize - https://www.nobelprize.org/prizes/chemistry/1987/summary/ (Accessed August 2026) VedPrep - https://www.vedprep.com/exams/uppsc/crown-ethers-in-s-block- elements/ (Accessed August 2026) S. Massa et al., Archiv der Pharmazie, 1993, 326, 539-546 G.G. Ramirez et al., Angew. Chem. Int. Ed. Engl., 2015, 54, 6110-6150 F. Stoddart et al., Eur. J. Org. Chem., 1998, 45, 2565-2571 Project Gallery

For this experiment, the gravitational acceleration was calculated by measuring the time period of a simple pendulum using three different experimental methods; methods 2 and 3 were more similar than method 1. This experiment is primarily for data analysis of the measurements taken of a simple pendulum oscillating freely to determine the acceleration due to gravity. Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Outline of an investigation of the period of a single pendulum, and its relation to gravity Last updated: 01/03/26 Last updated: 23/01/23 For this experiment, the gravitational acceleration was calculated by measuring the time period of a simple pendulum using three different experimental methods; methods 2 and 3 were more similar than method 1. This experiment is primarily for data analysis of the measurements taken of a simple pendulum oscillating freely to determine the acceleration due to gravity. This experiment can be repeated but can be carried out in different viscous liquids to see how the extra damping force affects the time period of the oscillation and calculate the g value from it. This can be useful to know as then making pendulum watches to work, say in different environments (such as under water), will be easier to make. It has future implications in industries and/ or technologies that produce related devices. Overall, this experiment was flawed from the beginning from not correctly applying the small angle criteria (in methods 2 and 3). However, there was success for method 1. (Reduced from a full lab report) Written by Siam Sama Related article: Viscosity of castor oil experiment