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Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Huntington's disease 07/02/25, 16:19 Last updated: Published: 18/10/23, 16:12 A hereditary neurodegenerative disorder Huntington’s disease (HD) is a neurodegenerative disorder causing cognitive decline, behavioural difficulties, and uncontrollable movements. It is a hereditary disease that has a devastating effect on the individual’s life and unfortunately is incurable. Genetic component What may come as a surprise, is that in everyone’s genetics there are two copies (one from each parent) of the Huntingtin’s gene coding for the Huntingtin protein. This gene is coded by CAG repeats. In healthy genes, the CAG sequence is repeated between 10 and 26 times. However, if the gene is faulty, CAG repeats over 40 times resulting in a dysfunctional Huntingtin protein. The disease is autosomal dominant meaning regardless of gender, if either parent is a carrier, their child has a 50% chance of inheriting the faulty gene. REMINDER: because the gene is dominant, it means those who inherit even one copy will develop the disease Effect on the brain The faulty Huntingtin protein accumulates in cells, leading to cell death and damage to the brain. If you were to look at the brains of individuals with Huntington’s Disease, you would see a reduction in volume of the caudate and putamen. These areas are part of the striatum, which is a subdivision of the basal ganglia, involved in fine tuning our voluntary movements, i.e., reaching out to grab a cup. As the disease progresses, this atrophy can extend to other areas of the brain including the thalamus, frontal lobe, and cerebellum. Symptoms The symptoms normally manifest in three categories: motor, cognitive and psychiatric. We know that the basal ganglia is involved in our voluntary movement, so the damage causes one of the most visible symptoms in HD- uncontrollable and jerky movements. Cognitive symptoms include personality changes, difficulties with planning and attention. There can also be impairments to how those with HD recognise emotions- all these symptoms can interact to make social interaction more difficult. Finally, the psychiatric symptoms often seen include irritability and aggression, depression, anxiety, and apathy. Impact on life and family At the age when diagnosis usually occurs (around 30 years old), patients are often buying houses, getting married and either having children or deciding to start a family. The diagnosis may change peoples outlook on having children and can put a great psychological burden on them if they have unknowingly passed it along to those already born. Diagnosis also brings consequences to seemingly mundane, but incredibly important issues such as gaining life insurance, with some companies not covering individuals with an official diagnosis. Subsequently this makes life harder for their families, as the patient will eventually be unable to work and there could be associated costs with the need for care facilities as the disease progresses. Unfortunately, this is a progressive neurodegenerative condition with no cure. The only treatment options available at present, are interventions which aim to alleviate the patients’ symptoms. Whilst these treatments will reduce the motor and psychiatric symptoms, they cannot stop the progression of Huntington’s disease. We have only scratched the surface on the impact Huntington’s disease has on a patient and their families. It is so important to understand ways in which everyone that is affected can be best supported during the disease progression, to give all those involved a better quality of life. Written by Alice Jayne Greenan Related article: Epilepsy Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unfolding prion diseases and their inheritance 12/04/24, 16:54 Last updated: Published: 06/03/24, 11:32 When misfolded proteins lead to disease Prion proteins are found abundantly in the brain; their function is unclear, but they are involved in a multitude of physiological mechanisms, including myelin homeostasis and the circadian rhythm. Correctly folded prion proteins in the cellular form are termed PrP C , while their infectious isoform is called PrP Sc . As shown in Figure 1, the misfolded PrP Sc is largely made up of β-pleated sheets instead of α-helices ; PrP Sc is prone to forming aggregates that cause transmissible spongiform encephalopathies (TSEs). Prion diseases can be categorised by their aetiology: acquired, sporadic, and hereditary. Acquired prion diseases are caused by the inadvertent introduction of PrP Sc prions into an individual. Sporadic prion diseases are the most common type, where PrP C misfolds into PrP Sc for an unknown reason and propagates this misfolding within other prion proteins. Hereditary prion diseases are caused by genetic mutation of the human prion protein gene (PRNP), which causes misfolding into the infectious isoform. Consequently, these mutations can be passed to offspring, resulting in the same misfolding and disease. Interestingly, different types of PRNP mutations cause different types of prion diseases. Creutzfeldt-Jakob disease (CJD) is a type of TSE found in humans which causes mental deterioration and involuntary muscle movement; symptoms tend to worsen as the disease progresses, making it a degenerative disorder. Familial CJD (fCJD) is a rare type of hereditary prion disease and can sometimes result in a faster rate of disease progression compared to sporadic cases. Due to a dominant inheritance pattern, relatives of fCJD patients are often also affected by the disease. The most common mutation observed in familial CJD is an E200K mutation denoting the substitution of glutamic acid with lysine in the prion protein. Other common mutations resulting in fCJD include mutations at positions 178 and 210 on the prion protein. However, there are, less frequently, a multitude of other mutations correlated with familial CJD development. Familial CJD can be caused by STOP codon mutations, which result in a truncated protein, some of which show similar pathology to Alzheimer’s disease, such as Q16OX and Q227X. fCJD can also be caused by insertional mutations, possibly caused by unbalanced crossover and recombination. The prion protein consists of a nona-peptide (made up of nine amino acids) followed by four repeats of an octa-peptide (made up of eight amino acids). During insertion mutations, additional repeats of the octa-peptide are present in the prion protein. Interestingly, different numbers of inserts result in different pathological characteristics; patients with 1, 2 or 4 extra repeats show similarity to sporadic CJD, while those with 5-9 extra repeats show similarity to Gerstmann-Sträussler-Scheinker syndrome. Hereditary prion diseases are important to study in order to develop an understanding of not only prion misfolding diseases but also diseases associated with misfolding of other proteins, such as Alzheimer’s and Parkinson’s. Understanding the mechanisms of hereditary prion diseases will aid the development of treatments for such conditions. In particular, observing and investigating particular genetic mutations observed to play a part in prion misfolding is crucial alongside using genetic information to infer the risk of disease an individual may have. Written by Isobel Cunningham Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Crohn's disease 06/02/25, 11:54 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

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can carbon monoxide unlock new pathways in inflammation therapy? 20/03/25, 12:03 Last updated: Published: 01/09/24, 10:31 Recent prospects for carbon monoxide indicate so Carbon monoxide (CO) is a colourless, odourless and tasteless gas which is a major product of the incomplete combustion of carbon-containing compounds. The toxic identity CO stems from its strong affinity for the haemoglobin in our blood which is around 300 times as strong as the affinity of oxygen. As a result, once the gas is inhaled, CO binds to the haemoglobin instead and reduces the amount of oxygen our blood can transport, which can cause hypoxia (low levels of oxygen in tissue) and dizziness, eventually leading to death. However, an intriguing fact is that CO is also endogenously produced in our body, due to the degradation of haem in the blood. Moreover, recent prospects for CO indicate that it may even be developed as an anti-inflammatory drug. How CO is produced in the body See Figure 1 Haem is a prosthetic (non-peptide) group in haemoglobin, where the oxygen binds to the iron in the molecule. When red blood cells reach the end of their lifespan of around 120 days, they are broken down in a reaction called haemolysis. This occurs in the bone marrow by macrophages that engulf the cells, which contain the necessary haem-oxygenase enzyme. Haem-oxygenase converts haem into CO, along with Fe2+ and biliverdin, the latter being converted to bilirubin for excretion. The breakdown of haem is crucial because the molecule is pro-oxidant. Therefore, free haem in the blood can lead to oxidative stress in cells, potentially resulting in cancers. Haem degradation also contributes to the recycling of iron for the synthesis of new haem molecules or proteins like myoglobin. This is crucial for maintaining iron homeostasis in the body. The flow map illustrates haemolysis and the products produced, which either protect cells from further stress or result in cell injury. CO can go on to induce anti-inflammatory effects- see Figure 2 . Protein kinases and CO Understanding protein kinases is crucial before exploring carbon monoxide (CO) reactions. Protein kinases phosphorylate (add a phosphate group to) proteins using ATP. Protein kinases are necessary to signal the release of a hormone or regulating cell growth. Each kinase has two regulatory (R) subunits and two catalytic (C) subunits. ATP as a reactant is usually sufficient for protein kinases. However, some kinases require additional mitogens – specific activating molecules like cytokines (proteins regulating immune cell growth), that are involved in regulating cell division and growth. Without the activating molecules, the R subunits bind tightly to the C subunits, preventing phosphorylation. Research on obese mice showed that CO binding to a Mitogen-Activated Protein Kinase (MAPK) called p38 inhibits inflammatory responses. This kinase pathway enhances insulin sensitivity, reducing obesity effects. The studies used gene therapy, modifying haem-oxygenase levels in mice. Mice with reduced haem-oxygenase levels had more adipocytes (fat-storing cells) and increased insulin resistance, suggesting CO treatment potential for chronic obstructive pulmonary disease (COPD), which causes persistent lung inflammation and results in 3 million deaths annually. Carbon-monoxide-releasing molecules As a result of these advancements, specific CO-releasing molecules (CORMs) have been developed to release carbon monoxide at specific doses. Researchers are particularly interested in the ability of CORMs to regulate oxidative stress and improve outcomes in conditions during organ transplantation, and cardiovascular diseases. Advances in the design of CORMs have focused on improving their stability, and targeted release to specific tissues or cellular environments. For instance, CORMs based on transition metals like ruthenium, manganese, and iron have been developed to enhance their efficacy and minimize side effects. This is achieved through carbon monoxide forming a stable ‘ligand’ structure with metals to travel in the bloodstream. Under an exposure to light or a chemical, or even by natural breakdown, these structures can slowly distribute CO molecules. Although the current research did not find any notable side effects within mouse cells, this does not reflect the mechanisms in human organ systems, therefore there is still a major risk of incompatibility due to water insolubility and toxicity issues. These problems could lead to potentially lead to disruption in the cell cycle, which may promote neurodegenerative diseases. Conclusion: the future of carbon monoxide Carbon monoxide has transitioned from being a notorious toxin to a valuable therapeutic agent. Advances in CO-releasing molecules have enabled its safe and controlled use, elevating its anti-inflammatory and protective properties to treat various inflammatory conditions effectively. This shift underpins the potential of CO to revolutionise inflammation therapy. It is important to remember that while carbon monoxide-releasing molecules (CORMs) have potential in controlled therapeutic settings, carbon monoxide gas itself remains highly toxic and should be handled with extreme caution to avoid serious health risks. Written by Baraytuk Aydin Related articles: Schizophrenia, inflammation and ageing / Kawasaki disease REFERENCES Different Faces of the Heme-Heme Oxygenase System in Inflammation - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/The-colorimetric-actions-of-the-heme-HO-system-heme-oxygenase-mediated-heme-degradation_fig3_6531826 (accessed 11 Jul, 2024). Nath, K.A. (2006) Heme oxygenase-1: A provenance for cytoprotective pathways in the kidney and other tissues, Kidney International. Available at: https://www.sciencedirect.com/science/article/pii/S0085253815519595 (Accessed: 12 July 2024). Gáll, T. et al. (2020) ‘Therapeutic potential of carbon monoxide (CO) and hydrogen sulfide (H2S) in hemolytic and hemorrhagic vascular disorders—interaction between the heme oxygenase and H2S-producing systems’, International Journal of Molecular Sciences, 22(1), p. 47. doi:10.3390/ijms22010047. Venkat, A. (2024) Protein kinase, Wikipedia. Available at: https://en.wikipedia.org/wiki/Protein_kinase (Accessed: 12 July 2024). Goebel, U. and Wollborn, J. (2020) Carbon monoxide in intensive care medicine-time to start the therapeutic application?! - intensive care medicine experimental, SpringerOpen. Available at: https://icm-experimental.springeropen.com/articles/10.1186/s40635-020-0292-8 (Accessed: 07 July 2024). Bansal, S. et al. (2024) ‘Carbon monoxide as a potential therapeutic agent: A molecular analysis of its safety profiles’, Journal of Medicinal Chemistry, 67(12), pp. 9789–9815. doi:10.1021/acs.jmedchem.4c00823. DeSimone, C.A., Naqvi, S.L. and Tasker, S.Z. (2022) ‘Thiocormates: Tunable and cost‐effective carbon monoxide‐releasing molecules’, Chemistry – A European Journal, 28(41). doi:10.1002/chem.202201326. Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A deep dive into the hallmarks defining Alzheimer’s disease 27/01/25, 16:32 Last updated: Published: 06/11/24, 12:02 Exploring the distinctive features that define and disrupt the brain The progressive decline in neurocognition, resulting in a detrimental effect on one’s activities of daily living, is referred to as dementia. It typically affects people over the age of 65. Multiple theories have been proposed to explain the pathogenesis of Alzheimer’s disease (AD), including the buildup of amyloid plaques in the brain and the formation of neurofibrillary tangles (NFT) in cells. Understanding the pathophysiology of AD is imperative to the development of therapeutic strategies. Therefore, this article will outline the major hallmarks and mechanisms of AD. Hallmark 1: amyloid plaques One of the most widely accepted hypotheses for AD is the accumulation of amyloid beta protein (Aβ) in the brain. Aβ is a 4.2 kDa peptide consisting of approximately 40–42 amino acids, originating from a precursor molecule called amyloid precursor protein. This process, defined as amyloidosis, is strongly linked to brain aging and neurocognitive decline. How do the amyloid plaques form? See Figure 1 . Reasons for the accumulation of amyloid plaques: Decreased autophagy: Amyloid proteins are abnormally folded proteins. Autophagy in the brain is primarily carried out by neuronal and glial cells, involving key structures known as autophagosomes and lysosomes. When autophagy becomes downregulated, the metabolism of Aβ is impaired, eventually resulting in plaque buildup. Overproduction of acetylcholinesterase (AChE): Acetylcholine (Ach) is the primary neurotransmitter involved in memory, awareness, and learning. Overproduction of ACHE by astrocytes into the synaptic cleft can lead to excessive breakdown of Ach, with detrimental effects on cognition. Reduced brain perfusion: Blood flow delivers necessary nutrients and oxygen for cellular function. Reduced perfusion can lead to “intracerebral starvation”, depriving cells of the energy needed to clear Aβ. Reduced expression of low-density lipoprotein receptor-related protein 1: Low-density lipoprotein receptor-related protein 1 (LRP1) receptors are abundant in the central nervous system under normal conditions. They are involved in speeding up the metabolic pathway of Aβ by binding to its precursor and transporting them from the central nervous system into the blood, thereby reducing buildup. Reduced LRP1 expression can hinder this process, leading to amyloid buildup. Increased expression of the receptor for advanced glycation end products (RAGE): RAGE is expressed on the endothelial cells of the BBB, and its interaction with Aβ facilitates the entry of Aβ into the brain. Hallmark 2: neurofibrillary tangles See Figure 2 Neurofibrillary tangles are excessive accumulations of tau protein. Microtubules typically support neurons by guiding nutrients from the soma (cell body) to the axons. Furthermore, tau proteins stabilise these microtubules. In AD, signalling pathways involving phosphorylation and dephosphorylation cause tau proteins to detach from microtubules and stick to each other, eventually forming tangles. This results in a disruption in synaptic communication of action potentials. However, the exact mechanism remains unclear. Recent studies suggest an interaction between Aβ and tau, where Aβ can cause tau to misfold and aggregate, forming neurofibrillary tangles inside brain cells. Both Aβ and tau can self-propagate, spreading their toxic effects throughout the brain. This creates a vicious cycle, where Aβ promotes tau toxicity, and toxic tau can further exacerbate the harmful effects of Aβ, ultimately causing significant damage to synapses and neurons in AD. Hallmark 3: neuroinflammation Microglia are the primary phagocytes in the central nervous system. They can be activated by dead cells and protein plaques, where they initiate the innate immune response. This involves the release of chemokines to attract other white blood cells and the activation of the complement system which is a group of proteins involved in initiating inflammatory pathways to fight pathogens. In AD, microglia bind to Aβ via various receptors. Due to the substantial accumulation of Aβ, microglia are chronically activated, leading to sustained immune responses and neuroinflammation. Conclusion The contributions of amyloid beta plaques, neurofibrillary tangles and chronic neuroinflammation provide a framework for understanding the pathophysiology of AD. AD is a highly complex condition with unclear mechanisms. This calls for the need of continued research in the area as it is crucial for the development of effective treatments. Written by Blessing Amo-Konadu Related articles: Alzheimer's disease (an overview) / CRISPR-Cas9 to potentially treat AD REFERENCES 2024 Alzheimer’s Disease Facts and Figures. (2024). Alzheimer’s & dementia, 20(5). doi:https://doi.org/10.1002/alz.13809. A, C., Travers, P., Walport, M. and Shlomchik, M.J. (2001). The complement system and innate immunity. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK27100/ . Bloom, G.S. (2014). Amyloid-β and tau: the Trigger and Bullet in Alzheimer Disease Pathogenesis. JAMA neurology, [online] 71(4), pp.505–8. doi:https://doi.org/10.1001/jamaneurol.2013.5847. Braithwaite, S.P., Stock, J.B., Lombroso, P.J. and Nairn, A.C. (2012). Protein Phosphatases and Alzheimer’s Disease. Progress in molecular biology and translational science, [online] 106, pp.343–379. doi:https://doi.org/10.1016/B978-0-12-396456-4.00012-2. Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., Jacobs, A.H., Wyss-Coray, T., Vitorica, J., Ransohoff, R.M., Herrup, K., Frautschy, S.A., Finsen, B., Brown, G.C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A. and Petzold, G.C. (2015). Neuroinflammation in Alzheimer’s disease. The Lancet. Neurology, 14(4), pp.388–405. doi:https://doi.org/10.1016/S1474-4422(15)70016-5. Kempf, S. and Metaxas, A. (2016). Neurofibrillary Tangles in Alzheimer′s disease: Elucidation of the Molecular Mechanism by Immunohistochemistry and Tau Protein phospho- proteomics. Neural Regeneration Research, 11(10), p.1579. doi:https://doi.org/10.4103/1673-5374.193234. Kumar, A., Tsao, J.W., Sidhu, J. and Goyal, A. (2022). Alzheimer disease. [online] National Library of Medicine. Available at: https://www.ncbi.nlm.nih.gov/books/NBK499922/. Ma, C., Hong, F. and Yang, S. (2022). Amyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules, 27(4), p.1210. doi:https://doi.org/10.3390/molecules27041210. National Institute on Aging (2024). What Happens to the Brain in Alzheimer’s Disease? [online] National Institute on Aging. Available at: https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain- alzheimers-disease. Stavoe, A.K.H. and Holzbaur, E.L.F. (2019). Autophagy in Neurons. Annual Review of Cell and Developmental Biology, 35(1), pp.477–500. doi: https://doi.org/10.1146/annurev-cellbio-100818-125242 . Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Decoding p53: the guardian against cancer 05/02/25, 16:21 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

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Are hydrogen cars the future of the UK? 16/01/25, 11:28 Last updated: Published: 01/01/25, 13:50 Hydrogen fuel cells generate electricity through an electrochemical reaction between hydrogen and oxygen Introduction With the London debut of the first ever hydrogen powered racing car in June 2024, the new off-road racing series, Extreme H, is set to make waves in the motorsport and sustainability industries with its first season in 2025. The first ever hydrogen powered motorsport series was announced in 2022 to replace the carbon-neutral electric racing series Extreme E, with the intention of pioneering the potential of hydrogen fuel cells and diversifying the paths of sustainable mobility. Like its predecessor, Extreme H will continue to race off-road in a spec SUV car, where engineers and machinists from competing teams optimise the SUV for the different range of terrains and topographies. The hydrogen spec SUV, fittingly called the Pioneer 25 ( Figure 1 ), is promising for the rapid advancement of hydrogen fuel research, leading to the integration of hydrogen fuel cells vehicles on local roads. In line with the upcoming ban on the sale of new petrol, diesel, and hybrid cars across the UK in 2035, as well as the UK target of reaching carbon neutral by 2050, the need for sustainable and practical transport options is growing. So far however, electric cars have proved to not be a one-size-fits-all solution. Hydrogen fuel could potentially be the key to filling this gap. EVs vs. HFCVs Working mechanisms Hydrogen Fuel Cell Vehicles (HFCVs): Hydrogen fuel cells generate electricity through an electrochemical reaction between hydrogen and oxygen. The electricity produced is used to power an electric motor, which drives the car. The only byproduct of this process is water vapour. Electric Vehicles (EVs): A motor is powered directly from a charged battery, and equally produces no harmful emissions. As a result of large investments, electric vehicles have already established a strong footing in the UK market, prompting the declining cost of batteries as well as increasing availability of EV charging points in the UK. However, for many households and commercial uses, electric vehicles are not accessible forms of transport due to key barriers including the extensive charging time (around 8 hours), the weight of batteries for large vehicles, and performance decline in cold weather due to lithium-ion batteries being highly sensitive to temperature. HFCVs directly address these problems and present a sustainable and competitive alternative. As the refuelling process is the same as petrol and diesel cars, fuel tanks can be filled in the space of a few minutes and are notably weight efficient. A heavy-duty electric vehicle on the other hand can require a battery of around 7000 kg. Advantages of HFCVs: Significantly shorter refuelling times Can achieve 300-400 miles on a full tank Maintain performance in cold weather and under heavy loads Lighter and more energy-dense than electric vehicles Disadvantages: Expensive as they’re not yet widely available Lack of refuelling infrastructure The current primary method of hydrogen production produces CO2 as a byproduct Despite the key advantages hydrogen cars offer, there are currently only 2 available models of HFC cars in the UK, including the Toyota Mirai ( Figure 2 ) and the Hyundai Nexo SUV. As a result, there are currently fewer than 20 refuelling stations available nationwide, compared to the many thousands of charging points available across the country for electric vehicles. One of the main reasons why progress in hydrogen fuel production has been so delayed is because hydrogen, despite being the most abundant element in the universe, is only available on earth in compound form and needs to be extracted using chemical processes. The true sustainability of hydrogen production There are currently two main methods to extract hydrogen from nature, including steam-methane reforming and electrolysis. Hydrogen is colour-graded by production method to indicate whether it is renewable. Green/ yellow hydrogen The cleanest process for hydrogen production is electrolysis, where a current separates hydrogen from pure water. If the current is sourced from renewable energy, it’s known as green hydrogen. If it’s connected via the grid, then it’s called yellow hydrogen. The source of electricity is particularly important because the electrolysis process is about 75% efficient, which translates to higher costs yet cleaner air. Grey/ blue hydrogen Hydrogen can also be produced by treating natural gas or methane with hot steam. During this process, the methane splits into its four hydrogen atoms while one carbon atom bonds to oxygen and enters the atmosphere as carbon dioxide. This is known as grey hydrogen. If the carbon dioxide can be captured and stored via direct air capture, it’s called blue hydrogen. About 95% of all hydrogen in Europe is produced by methane steam reforming (grey and blue hydrogen), as it is very energy efficient and uses up lots of natural gas in the process, a resource that is quickly diminishing in importance and value as more and more households switch from gas boilers to heat pumps. Two percent of the world’s carbon emissions comes from the grey hydrogen process to produce ammonia for fertiliser and for steel production. For context, this is almost the same as the entire aviation industry. For HFCVs to be a truly sustainable alternative to combustion engines, green hydrogen via electrolysis (or another clean process) needs to be more widely available and economically viable. The UK’s plans for hydrogen As part of the UK hydrogen strategy ( Figure 3 ), the UK aims to reach up to 10GW or low carbon hydrogen production by 2030 (or equivalent to the amount of gas consumed by 3 million households in the UK annually). The government has allocated £240 million to develop hydrogen production and infrastructure. This is particularly for industry uses in the production of steel and cement, and for heavy goods vehicles (HGVs). Plans were also made to extend the use of hydrogen to heat homes, starting with ‘hydrogen village trials’ in 2025, to inform how 100% hydrogen communities would work, although this has understandably been met with local opposition. With greater research, information, and development into hydrogen for domestic uses, the applications of hydrogen energy may extend from industry and transport to households. As car companies (particularly Toyota, Hyundai, and BMW) continue to develop hydrogen car makes, and further investment is made into increased refuelling infrastructure and hydrogen fuel cell research, as well as with the ban on the sale of new combustion engine cars by 2035, commercial hydrogen cars have the potential to be commonly found on UK roads by 2040. Conclusion For now, HFCVs remain in the early stages of development, however they present a promising opportunity for the UK to diversify its clean transport options, particularly in areas where EV technology faces limitations such as for heavy goods vehicles. Rather than being competitors, it is likely that EVs and HFCVs will soon coexist, with each technology serving different needs. The biggest barrier to the progress of HFCVs currently is developing a full hydrogen refuelling infrastructure, where the gas is produced and then transported to stations across the nation, will take billions of pounds and a number of years to develop. If these initial hurdles could be overcome, HFCV technology can quickly become more practically and financially accessible. Written by Varuna Ganeshamoorthy Related articles: Electric vehicles / Nuclear fusion Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The exciting potential of mRNA vaccines 14/02/25, 13:52 Last updated: Published: 03/12/24, 12:19 Unleashing the power of mRNA: revolutionising medicine with personalised vaccines Basic mRNA vaccine pharmacology Basic mRNA vaccine pharmacology involves the study of two types of RNA used as vaccines: non-replicating mRNA and self-amplifying RNA. Non-replicating mRNA-based vaccines encode the antigen of interest and contain untranslated regions (UTRs) at both ends. Self-amplifying RNAs, on the other hand, encode both the antigen and the viral replication machinery, allowing for intracellular RNA amplification and abundant protein expression. For successful protein production in mRNA therapeutics, the optimal translation of in vitro transcribed (IVT) mRNA is crucial. Factors such as the length of the poly(A) tail, codon usage, and sequence optimization can influence translation efficiency and accuracy. Adding an optimal length of poly(A) to mRNA is necessary for efficient translation. This can be achieved by directly incorporating it from the encoding DNA template or by using poly(A) polymerase. Codon usage also plays a role in protein translation. Replacing rare codons with frequently used synonymous codons, which have abundant cognate tRNA in the cytosol, can enhance protein production from mRNA. However, the accuracy of this model has been subject to questioning. Optimally translated IVT mRNA encoding mRNA IVT mRNA plays a crucial role in mRNA vaccines as it is designed for optimal translation, ensuring efficient protein production. To achieve this, a 5ʹ cap structure is added, which is essential for efficient protein synthesis. Different versions of 5ʹ caps can be added during or after the transcription process. Furthermore, the poly(A) tail plays a significant regulatory role in mRNA translation and stability. Sequence optimization is another critical factor that can enhance mRNA levels and protein expression. Increasing the G:C content has been shown to elevate steady-state mRNA levels in vitro and improve protein expression in vivo. Furthermore, modifying the codon composition or introducing modified nucleosides can positively influence protein expression. However, it is important to note that these sequence engineering techniques may impact mRNA secondary structure, translation kinetics, accuracy, protein folding, as well as the expression of alternative reading frames and cryptic T-cell epitopes. Sequence optimization for protein translation Sequence optimization plays a crucial role in the development of mRNA vaccines. It involves modifying the mRNA sequence to improve the efficiency of protein translation. By optimizing the sequence, researchers can enhance the expression and stability of therapeutic mRNAs. However, the immunogenicity of exogenous mRNA is a concern, as it can trigger a response from various innate immune receptors. In some cases, encoding mRNA in the hypothalamus may even elicit a physiological response. Despite initial promising outcomes, the development of mRNA therapeutics has been hindered by concerns regarding mRNA instability, high innate immunogenicity, and inefficient in vivo delivery. As a result, DNA-based and protein-based therapeutic approaches have been preferred in the past. Modulation of immunogenicity Modulation of immunogenicity is a crucial aspect of mRNA vaccine development. Researchers aim to design mRNA vaccines that elicit a strong immune response while minimizing adverse reactions. This involves careful selection of antigens and optimization of the mRNA sequence to enhance immunogenicity. Self-replicating RNA vaccines and adjuvant strategies, such as TriMix, have shown increased immunogenicity and effectiveness. The immunostimulatory properties of mRNA can be further enhanced by including adjuvants. The size of the mRNA-carrier complex and the level of innate immune sensing in targeted cell types can influence the immunogenicity of mRNA vaccines. Advantages of mRNA vaccines mRNA vaccines offer several advantages over conventional vaccine approaches. First, they have high potency, meaning they can induce a strong immune response. Second, they have a capacity for rapid development, allowing for quick vaccine production in response to emerging infectious diseases or new strains. Third, mRNA vaccines have the potential for rapid, inexpensive, and scalable manufacturing, mainly due to the high yields of in vitro transcription reactions. Additionally, mRNA vaccines are minimal genetic vectors, avoiding anti-vector immunity, and can be administered repeatedly. However, recent technological innovations and research investments have made mRNA a promising therapeutic tool in vaccine development and protein replacement therapy. mRNA has several advantages over other vaccine platforms, including safety and efficacy. It is non-infectious and non-integrating, reducing the risk of infection and insertional mutagenesis. mRNA can be regulated in terms of in vivo half-life and immunogenicity through various modifications and delivery methods. Production of mRNA vaccines The production of mRNA vaccines involves in vitro transcription (IVT) of the optimized mRNA sequence. This process allows for the rapid and scalable manufacturing of mRNA vaccines. High yields of IVT mRNA can be obtained, making the production process cost-effective. Making mRNA more stable and highly translatable is achievable through modifications. Efficient in vivo delivery can be achieved by formulating mRNA into carrier molecules. The choice of carrier and the size of the mRNA-carrier complex can also modulate the cytokine profile induced by mRNA delivery. Current mRNA vaccine approaches ( Figure 1 ) There are several current mRNA vaccine approaches being explored. These include the development of mRNA vaccines against infectious diseases and various types of cancer. mRNA vaccines have shown promising results in both animal models and humans. Cancer vaccines Cancer vaccines are a type of immunotherapy that aim to stimulate the body's immune system to recognize and destroy cancer cells. These vaccines work by introducing specific antigens, which are substances that can stimulate an immune response, into the body. The immune system then recognizes these antigens as foreign and mounts an immune response against them, targeting and destroying cancer cells that express these antigens. There are different types of cancer vaccines, including personalized vaccines and predefined shared antigen vaccines. Personalized vaccines are tailored to each patient and are designed to target specific mutations or antigens present in their tumor. These vaccines are created by identifying tumor-specific antigens by sequencing the patient's tumor DNA and predicting which antigens are most likely to elicit an immune response. These antigens are then used to create a vaccine that is specific to that patient's tumor. On the other hand, predefined shared antigen vaccines are designed to target antigens that are commonly expressed in certain types of cancer. These vaccines can be used in multiple patients with the same type of cancer and are not personalized to each individual. The antigens used in these vaccines are selected based on their ability to induce an immune response and their potential to be recognized by T cells. Despite the promising potential of cancer vaccines, their clinical progress is limited, and skepticism surrounds their effectiveness. While there have been some examples of vaccines that have shown systemic regression of tumors and prolonged survival in small clinical trials, many trials have yielded marginal survival benefits. Challenges such as small trial sizes, resource-intensive approaches, and immune escape of heterogeneous tumors have hindered the field's progress. However, it is important to note that other immunotherapies, such as monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies, have also faced challenges and setbacks before eventually achieving success. Therefore, cancer vaccines may also have the potential for eventual success, given their clear rationale and compelling preclinical data. To improve the efficacy of cancer vaccines, researchers are exploring various strategies. These include optimizing antigen presentation and immune activation by using adjuvants or agonists of pattern-recognition receptors. Additionally, advancements in sequencing technologies and computational algorithms for epitope prediction allow for the identification of more specific tumor mutagens and the production of personalized neo-epitope vaccines. Neo-epitope vaccines are a type of personalized vaccine that target specific mutations or neo-epitopes present in a patient's tumor. These vaccines exploit the most specific tumor mutagens identified through computational methods and prioritize highly expressed neo-epitopes. They can be given with adjuvants to enhance their immunogenicity. Hence, cancer vaccines hold promise as a potential standard anti-cancer therapy. While their progress has been limited, a clear rationale and compelling preclinical data support their further development. Personalized vaccines targeting specific mutations or antigens present in a patient's tumor, as well as predefined shared antigen vaccines targeting commonly expressed antigens, are being explored. Future of mRNA vaccines mRNA vaccines have emerged as a promising alternative to traditional vaccine approaches due to their high potency, rapid development capabilities, and potential for low-cost manufacture and safe administration. Recent technological advancements have addressed the challenges of mRNA instability and inefficient in vivo delivery, leading to encouraging results in the development of mRNA vaccine platforms against infectious diseases and various types of cancer. Looking ahead, the future of mRNA vaccines holds great potential for further advancements and widespread therapeutic use. Efficient in vivo delivery of mRNA remains a critical area of focus for future development. Researchers are working on improving delivery systems to ensure targeted delivery to specific cells or tissues, thereby enhancing the effectiveness of mRNA vaccines. This includes the development of lipid nanoparticles, viral vectors, and other delivery mechanisms to optimize mRNA delivery and cellular uptake. The success of mRNA vaccines against infectious diseases and cancer has opened doors to exploring their potential in other areas of medicine. Future research may involve the development of mRNA vaccines for autoimmune disorders, allergies, and chronic diseases. The versatility of mRNA technology allows for the rapid adaptation of vaccine candidates to address various medical conditions. One exciting prospect for mRNA vaccines is their potential for personalized medicine. The ability to easily modify the genetic sequence of mRNA allows for the development of personalized vaccines tailored to an individual's specific genetic makeup or disease profile. This could revolutionize preventive medicine by enabling targeted immunization strategies. Combining mRNA vaccines with other treatment modalities, such as immunotherapies or traditional therapies, could lead to synergistic effects and improved clinical outcomes. The unique properties of mRNA vaccines, such as their ability to induce potent immune responses and modulate the expression of specific proteins, make them attractive candidates for combination therapies. Continued advancements in manufacturing processes will be crucial for the widespread adoption of mRNA vaccines. Efforts are underway to optimize and scale up the production of mRNA vaccines, making them more accessible and cost-effective. This includes refining in vitro transcription reactions and implementing efficient quality control measures. The regulatory landscape surrounding mRNA vaccines will evolve as the field progresses. Regulatory agencies will need to establish guidelines and frameworks specific to mRNA vaccine development and approval. Ensuring safety, efficacy, and quality control will be essential to gain widespread acceptance and public trust in mRNA vaccines. Conclusion mRNA vaccines have shown great potential in revolutionizing the field of medicine, particularly in the areas of personalized medicine and preventive medicine. The ability to easily modify the genetic sequence of mRNA allows for the development of personalized vaccines tailored to an individual's specific genetic makeup or disease profile. Furthermore, the unique properties of mRNA vaccines, such as their ability to induce potent immune responses and modulate the expression of specific proteins, make them attractive candidates for combination therapies. However, there are still challenges to overcome, such as ensuring safety, efficacy, quality control, addressing concerns regarding immunogenicity. Nonetheless, with continued advancements in manufacturing processes and regulatory guidelines, the future of mRNA vaccines holds great promise for further advancements and widespread therapeutic use. Efforts to improve in vivo delivery systems and explore the potential of mRNA vaccines in other areas of medicine, such as autoimmune disorders and chronic diseases, further contribute to the promising outlook for this technology. Written by Sara Maria Majernikova Related articles: Potential malaria vaccine / Bioinformatics in COVID vaccine production / Personalised medicine REFERENCES Lin, M.J., Svensson-Arvelund, J., Lubitz, G.S. et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer 3, 911–926 (2022). https://doi.org/10.1038/s43018-022-00418-6 Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17 , 261–279 (2018). DOI: https://doi.org/10.1038/nrd.2017.243 Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The game of life 14/02/25, 13:54 Last updated: Published: 20/11/23, 11:22 Maths till 18? No! All subjects till 18! I am a Maths graduate, a Maths teacher, and an all-rounder academic, yet in my twenties, when I began the process of buying a home, I had no idea where to start. I did not know how to get a mortgage, what shared ownership was, or when to get a solicitor involved. This is a problem, and this, I believe, is what needs to be taught from 16-18 years of age. The skills, opportunities, and options for young adults to simply move forward in this world. My suggestion: (for those who do not take A-Levels) To create a well-structured, virtual reality, cross-curricular running project about life, a little bit like an AI version of the ‘game of life.’ Students can begin the project in a virtual reality world of choice, and then slowly branch out depending on their interests. They can learn CV building skills , go to an AI job centre, choose the job they want to do and learn the skills for it by conducting research and completing online courses . At the same time within the project, students can be given a budget according to the job they are training for, in which they can forecast their savings and plan for the route that they would take in purchasing a property. Students would need to learn about shared ownership, the pros and cons of renting, the deposits needed for mortgage, all within a game format, like a PS5 game. This aspect of the project would be heavy with Maths. Students would be expected to write a final assessment piece summarising each of their decisions and why, which would include high levels of the English curriculum. To differentiate the project, we could ask students to use Geography, to find a country in the world where their skills may be more in demand and ask them to consider the possibility of relocating to another country for work, which would broaden the horizon of the project massively. They could look at tax laws in different countries, such as Dubai, and how that would benefit them in terms of salary, but what the importance of tax is in a country too. Students would get to explore countries which have free healthcare and schooling vs which countries do not. This would work on their analysis and deeper thinking skills. The game-like format of this project would be ideal for disengaged students who did not thrive with the traditional style of teaching in schools. We could include potential for earning points in the ‘game’ for each additional piece of research they conduct, and a real-life benefit to earning those points too, such as Amazon vouchers, as rewards. A project like this would enable all curriculums to get involved in, for students to understand the world better and a massive scope for AI, potentially asking Meta to design it, who are at the forefront of virtual reality. To make it work, the project would require teachers from all fields to come together to form a curriculum that is inclusive, considers British Values and mirrors the real-life that we live in today. There is potential for psychologist to be involved to ensure we are considering mental health implications as well as parents/guardians, who would need to be onboard with this too. In conclusion, I believe that 16-18 years do need guided learning that is standardised, but I do not think it is as simple as pushing Maths on to them. The future generation and their society will benefit from a holistic guided route to life, which will make them informed and educated individuals in topics that matter to THEM, based on THEIR lives, not chosen by us. Give students control over their education, over their lives... Written by Sara Altaf Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can Tetris help treat Post Traumatic Stress Disorder? 02/11/24, 11:47 Last updated: Published: 06/03/24, 11:47 PTSD and Tetris This is the last part (Part II) in the two-part series on PTSD and intrusive memories, discussing how a common and well-loved visuospatial game, Tetris, can reduce the presence of the core clinical symptom. Previous article: Boom, and you're back! As discussed in an earlier article , psychological trauma resulting from threat to life or serious injury from events such as vehicle accidents or assault, among others, can result in development of post traumatic stress disorder (PTSD). The core clinical feature is intrusive memories, where memories of the event involuntarily intrude into a person’s consciousness after being triggered by environmental cues, resulting in extreme emotional distress. Two of the most common and effective treatments for PTSD include trauma-focused cognitive behavioural therapy (CBT) and eye movement desensitisation and reprocessing (EMDR) therapy. These approaches address an individual’s memory of the event alongside their emotional understanding of the experience. Unfortunately, there is a lack of qualified therapists and patients are often wary of delving into the event details. This results in many patients not receiving sufficient treatment. Following an event, the memory must be consolidated into long-term memory for it to be remembered at a later date. Memory consolidation theory states that the memory is flexible several hours following the event, meaning it can be interfered with. Engaging in a visuospatial task during this period may weaken the consolidation of the traumatic memory because the tasks compete with limited cognitive resources. Therefore, completing tasks with high visuospatial demands in the consolidation period may reduce the occurrence of intrusive memories. Many studies have looked into this, using Tetris to disrupt the memory up to six hours post exposure, and have found positive results. One study took this outside of the laboratory, recruiting patients in an emergency department following serious vehicle accidents. The intervention involved two steps, first patients were asked to remember the accident and state the most traumatising experience they observed. Following this they played Tetris for a minimum of 10 minutes, which competed with the visual memories they had just produced. It was found that 62% of those in the Tetris intervention group had a reduction in intrusive memories in the subsequent week, compared to those in the control group. However, it is not always practical to play a video game in the direct aftermath of the event. The memory consolidation theory also states that memories become flexible to change when they are remembered and subsequently must be reconsolidated into long-term memory. Therefore, other studies have investigated using Tetris as an intervention for those already experiencing PTSD. In this case, combining Testis game play with EMDR therapy has been found useful. After completion of therapy, both control and Tetris groups were found to have a reduction in symptoms at 6-months. However, only the Tetris group had reductions in anxiety and depression. Remember in the previous article we spoke about the neuroanatomy of PTSD and how that related to intrusive memories. Research has shown those with PTSD have reductions in hippocampus and ventromedial prefrontal cortex volume, with the reduced hippocampal volume correlating to symptom severity. In fact, studies investigating the use of Tetris have shown that playing this during psychological therapy increases the hippocampal volume, and this increase correlates to the reduced symptoms 6-months following treatment. Currently, the interventions for PTSD have limitations surrounding the longevity of symptom improvements. Therefore, combining Tetris playing with psychotherapies may maintain the symptom improvements long term by increasing the hippocampal volume. Not only this, but videogames with high visuospatial demands like Tetris, may provide some utility as preventative interventions, which are currently lacking. Considering patients involved in vehicle accidents wait upto four hours in emergency departments in the UK, there is an opportunity to reach patients within the memory consolidation window. This approach is not only cost-effective and requires straightforward training for implementation but has been found acceptable in clinical populations. Notably, the earlier study found 48% of patients engaged in this approach, surpassing participation rates of 10% in a psychotherapy trial and 8% in a pharmacological trial within the same emergency department. Overall, interfering with memory consolidation using Tetris could provide a good treatment option for intrusive memories in PTSD. So, where are we currently? Research is still being undertaken, with some even investigating the effects of other visuospatial games such as Candy Crush. Written by Alice Jayne Greenan Project Gallery