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A problem synthesising haem Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Sideroblastic anaemia 11/07/25, 09:52 Last updated: Published: 22/12/23, 15:20 A problem synthesising haem This is the fourth and final article in a series about anaemia. First article: anaemia . Previous article: Anaemia of chronic disease . Sideroblastic anaemia (SA) is like haemochromatosis as there is too much iron. Due to an absence of protoporphyrin iron transport is inhibited. SA’s include hereditary and acquired conditions; these can be due to alcohol, toxins, congenital defects, malignancies, or mutations. This haem synthesizing defect can be caused by the X-linked chromosome or the lead poisoning induced mutations, these are main mutations that interrupt the 8 enzymatic cascades in the biosynthesis of protoporphyrin, thus leading to defective haemoglobin (Hg) moreover, iron accumulation in the mitochondria. X-linked protoporphyria is due to a germline mutation in the gene that produces δ-aminolaevulinic acid (δ-ala) synthase, this interrupts the first step of haem synthesis, figure 1. Lead poisoning can interrupt 2 stages of haem synthesis δ-ala dehydratase (-δ-ala dehydratase porphyria) and ferrochelatase (erythropoietic protoporphyria). The first step devastates the production of haem, due to the chromosomal abnormality that stops the production of δ-ala dehydratase, is X-linked porphyria. The second step and the final step are associated with lead poisoning, this is more common in children. Ferrochelatase is a catalyst for the incorporation of iron to haem in the final stage of haemoglobin synthesis, this causes ferrochelatase erythrocytic protoporphyrin (FECH EPP). SA clinical presentation Common features of SA are general to microcytic anaemias such as teardrop and hypochromic cells, dimorphism is common, pappenheimer bodies and mitochondrial iron clusters which are found in bone marrow smears, where iron accumulates around 2/3 of the nucleus of erythroblasts. Without knowing the aetiology of anaemia standard FBCs and iron studies would be run to initially diagnosis the anaemia, with SA the iron cannot be transported so transferrin will be reduced, alongside mean cell volume (MCV), haemoglobin and haematocrit (HCT). There will also be an increase in ferratin, % saturation and serum Fe. Microcytic anaemia presents in 20-60% of patients with FECH-EPP. morphology will present as microcytic and hypochromic with the possible presentation of Pappenheimer bodies, ringed sideroblasts, dimorphism and basophilic stippling may be present in bloods of children suspected in lead >5 µg/dL. Lead poisoning can be misdiagnosed as porphyrin as lead is shed from the body slowly, this allows approximately 80% of the lead to be absorbed. Although lead exits the blood rather quickly once it’s in the bone it can have a half-life of 30 years. Written by Lauren Kelly Related articles: Blood / Kawasaki disease Project Gallery

Exenatide as a potential drug Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A common diabetes drug treating Parkinson’s disease 08/07/25, 14:37 Last updated: Published: 24/01/24, 21:15 Exenatide as a potential drug A new investigational drug, originally developed for type 2 diabetes, is being readied for human clinical trials in search of the world's first treatment to impede Parkinson's disease progression. Parkinson's (PD) is the second most common neurodegenerative disorder. The connection between type 2 diabetes (T2DM) and PD was discovered in 1993, when PD patients with co-existing T2DM had worse motor symptoms and response to therapy. Dopaminergic neurons promote eating behaviour in hypoglycaemic states, mediated via insulin receptors in the substantia nigra, because dopaminergic neuronal loss affects glycaemic control. Thus, T2DM patients are more likely to acquire PD than people without diabetes. Excess glucose in the brain, as found in uncontrolled T2DM, may interact randomly with surrounding proteins and interfere with their function. These interactions also result in toxic end products promoting inflammation and α-synuclein clustering, both of which are PD characteristics. Over a 12-year period, retrospective data (N=8,190,323) showed that T2DM responders had considerably greater PD rates when compared to those without diabetes. The rise was significantly more pronounced among individuals with complex T2DM and those aged 25-44. Exenatide: Overview and Mechanism of Action Exenatide is a synthetic form of exendin-4, a naturally occurring protein identified in the saliva of the Gila monster (poisonous lizard endemic to the Southwest US) by Dr. Eng in the early 1990s. In humans, the chemical is produced after a meal to increase insulin production, decreasing blood sugar. GLP-1 degrades fast in humans, and its benefits are short-lived. However, investigations have shown effects of exendin-4 continue longer in people. This finally led to FDA clearance in 2005, when the product was sold as Byetta TM . Its current indications are for the treatment of balancing glucose levels in T2DM with or without additional oral hypoglycemic medications. This glycaemic control is an analogue of human GLP-1, used in T2DM treatment, either alone or in conjunction with other antidiabetic medications. Exendin-4's neuroprotective characteristics may aid in rescuing degenerating cells and neuron protection. Because T2DM and PD are linked, researchers want to explore its effectiveness as a PD therapy. Patients treated with exenatide for one year (in addition to standard medication) experienced less deterioration in motor symptoms when tested without medication compared to the control group. Research on Exenatide as a Potential Parkinson's Disease Therapy 21 patients with intermediate PD were assessed over a 14-month period, and their progress was compared to 24 other people with Parkinson's who served as controls. Exenatide was well accepted by participants, albeit some individuals complained about weight loss. Significantly, exenatide-treated participants improved their PD movement symptoms, while the control patients continued to deteriorate. The researchers investigate exenatide, a possible PD therapy, in an upcoming clinical study, lending support to the repurposing of diabetes drugs for Parkinson's patients. This research adds to the evidence for a phase 3 clinical trial of exenatide for PD patients. Data on 100,288 T2DM revealed that people using two types of diabetic medications, GLP-1 agonists and DPP4-inhibitors, were less likely to be diagnosed with Parkinson's up to 3.3 years follow-up. Those who used GLP-1 agonists were 60% less likely to acquire PD than those who did not. The results revealed that T2DM had a higher risk of Parkinson's than those without diabetes, although routinely given medicines, GLP-1 agonists, and DPP4-inhibitors seemed to reverse the association. Furthermore, a 2-year follow-up research indicated individuals previously exposed to exenatide displayed a substantial improvement in their motor characteristics 12 months after they ceased taking the medication. However, this experiment was an open-label research so the gains may be explained by a placebo effect. The research adds to the evidence that exenatide may assist to prevent or treat PD, perhaps by altering the course of the illness rather than just lowering symptoms. Other risk factors for PD should be considered by clinicians when prescribing T2DM drugs, although further study is required to clarify clinical significance. Findings from Clinical Trials and Studies Based on these findings, the UCL team broadened their investigation and conducted a more extensive, double-blind, placebo-controlled experiment. The findings establish the groundwork for a new generation of PD medicines, but they also confirm the repurposing of a commercially existing therapy for this illness. Patients were randomly randomised (1:1) to receive exenatide 2 mg or placebo subcutaneous injections once weekly in addition to their current medication for 48 weeks, followed by a 12-week washout period. Web-based randomisation was used, with a two-stratum block design depending on illness severity. Treatment allocation was concealed from both patients and investigators. The main outcome was the adjusted difference in the motor subscale of the Movement Disorders Society Unified Parkinson's Disease Rating Scale after 60 weeks in the realistically defined off-medication condition. Six major adverse events occurred in the exenatide group and two in the placebo group, but none were deemed to be connected to the research treatments in either group. It is unclear if exenatide alters the underlying illness mechanism or causes long-term clinical consequences. Implications and Future Directions Indeed, the UCL study showed that exenatide decreases deterioration compared to a placebo. However, participants reported no change in their quality of life. The study team would broaden their study to include a broader sample of people from several locations. Because PD proceeds slowly, longer-term trials might provide a better understanding of how exenatide works in these responders. Overall, findings suggest that gathering data on this class of medications should be the topic of additional inquiry to evaluate their potential. Exenatide is also being studied to see whether it might postpone the onset of levodopa-induced problems (e.g., dyskinesias). Furthermore, if exenatide works for Parkinson's, why not for other neurodegenerative illnesses (Alzheimer's, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis) or neurological diseases (including cerebrovascular disorders, traumatic brain injury...)? Exenatide has been FDA-approved for diabetes for many years and has a good track record, but it does have some adverse side effects in Parkinson's patients, namely gastrointestinal difficulties (nausea, constipation). Exenatide as a prospective PD therapy is an example of medication repurposing or repositioning, an essential method for bringing novel therapies to patients in a timely and cost-effectively. However, further research is required, so it will be many years before a new therapy is licenced and available. Drug repurposing, or using authorised medicines for one ailment to treat another, opens up new paths for Parkinson's therapeutic development. Conclusion Exenatide shows potential as a therapy for Parkinson's disease (PD). Studies have shown that exenatide may help improve motor symptoms and slow down the progression of PD. However, further research and clinical trials are needed to fully understand its effectiveness and long-term effects. The findings also suggest that repurposing existing medications, like exenatide, could provide new avenues for developing PD therapies. While exenatide shows promise, it will likely be many years before it is licensed and widely available as a PD treatment. PROJECT GALLERY IMAGES DESCRIPTION Figure 1- The use of GLP-1 is beyond diabetes treatment. Nineteen clinical studies found that GLP-1 agonists can improve motor scores in Parkinson's Disease, improve glucose metabolism in Alzheimer's, and improve quality of. They can also treat chemical dependency, improve lipotoxicity, and reduce insulin resistance. However, adverse effects are primarily gastrointestinal. Thus, GLP-1 analogues may be beneficial for other conditions beyond diabetes and obesity. Figure 2- Potent GLP-1 agonists suppress appetite through a variety of mechanisms, including delayed gastric emptying, increased glucose-dependent insulin secretion, decreased glucagon levels, and decreased food ingestion via central nervous system effects. Short-acting agents, including exenatide, primarily function by impeding gastric evacuation, thereby leading to a decrease in postprandial glucose levels. On the contrary, extended-release exenatide and other long-acting agonists (e.g., albiglutide, dulaglutide) exert a more pronounced impact on fasting glucose levels reduction via their mechanism of action involving the release of insulin and glucagon. The ineffectiveness of long-acting GLP-1 receptor agonists on gastric evacuation can be attributed to the development of tolerance to GLP-1 effects, which is regulated by parasympathetic tone alterations. Figure 3- Illustrated is the cross-communication with insulin receptor signalling pathways and downstream effectors . Biomarkers can be derived from the formation and origin of extracellular vesicles, which indicate the initial inward budding of the plasma membrane. An early endosome is formed when this membrane fuses; it subsequently accumulates cytoplasmic molecules. As a consequence, multivesicular bodies are generated, which subsequently fuse with the plasma membrane and discharge their constituents into the extracellular milieu. Akt denotes protein kinase B; Bcl-2 signifies extracellular signal-related kinase; Bcl-2 antagonist of death; Bcl-2 extra large; Bcl-XL signifies Bcl-2; Bim signifies Bcl-2-like protein 11; cAMP signifies cyclic adenosine monophosphate; CREB signifies cAMP response element-binding protein; Erk1/2 signifies extracellular signal-related kinase IDE, insulin-degrading enzyme; IL-1α, interleukin 1α; IRS-1, insulin receptor signalling substrate 1; MAPK, mitogen-associated protein kinase; mTOR, mechanistic target of rapamycin; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; NF-kB, nuclear factor–κB; PI3-K, phosphoinositide 3-kinase; PKA, protein kinase; FoxO1/O3, forkhead box O1/O3, forkhead box O1/O3; GRB2, growth factor receptor-bound protein 2; GSK-3β, Written by Sara Maria Majernikova Related articles: Pre-diabetes / Will diabetes mellitus become an epidemic? / Parkinson's risk / Markers for Parkinsonism Project Gallery

From the Big Bang to the current model Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Story of the atom 11/02/25, 12:23 Last updated: Published: 20/04/24, 11:16 From the Big Bang to the current model The Greek philosopher and physicist Democritus proposed the idea of an atom at around 440 B.C. The atom is first explained by him using a stone. When a stone is split in half, it becomes two separate stones. There would eventually come to be a portion of the stone that would be too small to be cut if it were to be cut continuously i.e., indivisible. Since then, many scientists have adopted, discarded, or published their own theories about the nature, structure, and size of atoms. However, the most widely accepted, and still the basic model used to study atoms is Rutherford’s model. Rutherford published his theory of the atom suggesting that it had an electron orbiting a positively charged nucleus. This model was created after a series of experiments which included shooting alpha particles at thin gold sheets. Most of the alpha particles flowed through with little disturbance, but a tiny fraction was scattered at extreme angles to their initial direction of motion. Rutherford calculated the estimated size of the gold atom's nucleus and discovered that it was at least 10,000 times smaller than the atom's total size, with a large portion of the atom made up of empty space. This theory paved the way to further the atomic models by various other scientists. (Figure 1) Researchers have discovered unidentified molecules in space which are believed to be the precursor of all chemistry in the universe. The earliest "atoms" in the cosmos were actually nuclei without any electrons. The universe was incredibly hot and dense in the earliest seconds following the Big Bang. The quarks and electrons that make up matter first appeared when the cosmos cooled, and the ideal conditions were met for them to do so. Protons and neutrons were created by quarks aggregating a few millionths of a second later. These protons and neutrons joined to form nuclei in a matter of minutes. (Figure 2) Things started to happen more slowly as the cosmos cooled and expanded. The first atoms were formed 380,000 years ago when electrons were locked into orbits around nuclei. These were mostly hydrogen and helium, which are still the elements that are found in the universe in the greatest quantities. Even now, the most basic nucleus, found in ordinary hydrogen, is only a single, unadorned proton. There were other configurations of protons and neutrons that also developed, but since the number of protons in an atom determines its identity, all these other conglomerations were essentially just variations of hydrogen, helium, and lithium traces. To say that this is an exciting time for astrochemistry is an understatement. Furthermore, the formation mechanism of amino acids and nucleobases is being demonstrated by laboratory simulations of interstellar environments. Now that we are finding answers to these known problems, even more are arising. Hopefully, a more thorough understanding of these chemical processes will enable us to make more precise deductions about the general history of the universe and astrophysics. Written by Navnidhi Sharma REFERENCES CERN (n.d.). The early universe. [online] CERN. Available at: https://home.cern/science/physics/earlyuniverse#:~:text=As%20the%20universe%20continued%20to . Compound Interest (2016). The History of the Atom – Theories and Models | Compound Interest. [online] Compound Interest. Available at: https://www.compoundchem.com/2016/10/13/atomicmodels/ . Fortenberry, R.C. (2020). The First Molecule in the Universe. Scientific American. [online] doi: https://doi.org/10.1038/scientificamerican0220-58 . Sharp, T. (2017). What is an Atom? [online] Live Science. Available at: https://www.livescience.com/37206-atom-definition.html . Project Gallery

The maths behind trading Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A comprehensive guide to the Relative Strength Index (RSI) 08/07/25, 14:37 Last updated: Published: 27/12/23, 11:02 The maths behind trading In this piece, we will delve into the essential concepts surrounding the Relative Strength Index (RSI). The RSI serves as a gauge for assessing the strength of price momentum and offers insights into whether a particular stock is in an overbought or oversold condition. Throughout this exploration, we will demystify the underlying calculations of RSI, explore its significance in evaluating market momentum, and unveil its practical applications for traders. From discerning opportune moments to buy or sell based on RSI values to identifying potential shifts in market trends, we will unravel the mathematical intricacies that underpin this critical trading indicator. Please note that none of the below content should be used as financial advice, but for educational purposes only. This article does not recommend that investors base their decisions on technical analysis alone. As indicated in the name, RSI measures the strength of a stock's momentum and can be used to show when a stock can be considered over- or under-bought, allowing us to make a more informed decision as to whether we should enter a position or hold off until a bit longer. It’s all very well and good to know that ‘you should buy when RSI is under 30 and sell when RSI is over 70' , but in this article, I will attempt to explain why this is the case and what RSI is really measuring. The calculations The relative strength index is an index of the relative strength of momentum in a market. This means that its values range from 0 to 100 and are simply a normalised relative strength. But what is the relative strength of momentum? Initial Average Gain = Sum of gains over the past 14 days / 14 Initial Average Loss = Sum of losses over the past 14 days / 14 Relative strength is the ratio of higher closes to lower closes. Over a fixed period of usually 14 days (but sometimes 21), we measure how much the price of the stock has increased in each trading day and find the mean average between them. We then repeat and do the same to find the average loss. The subsequent average gains and losses can then be calculated: Average Gain = [(Previous Avg. Gain * 13) + Current Day's Gain] / 14 Average Loss = [(Previous Avg. Loss * 13) + Current Day's Loss] / 14 With this, we can now calculate relative strength! Therefore, if our stock gained more than it lost in the past 14 days, then our RS value would be >1. On the other hand, if we lost more than we gained, then our RS value would be <1. Relative strength tells us whether buyers or sellers are in control of the price. If buyers were in control, then the average gain would be greater than the average loss, so the relative strength would be greater than 1. In a bearish market, if this begins to happen, we can say that there is an increase in buyers’ momentum; the momentum is strengthening. We can normalise relative strength into an index using the following equation: Relative Strength= Average Gain / Average Loss Traders then use the RSI in combination with other techniques to assess whether to buy or sell. When a market is ranging, which means that price is bouncing between support and resistance (has the same highs and lows for a period), we can use the RSI to see when we may be entering a trend. When the RSI is reaching 70, it is an indication that the price is being overbought, and in a ranging market, there is likely to be a correction and the price will fall so that the RSI stays at around 50. The opposite is likely to happen when the RSI dips to 30. Price action is deemed to be extreme, and a correction is likely. It should, however, be noted that this type of behaviour is only likely in assets presenting mean-reversion characteristics. In a trending market, RSI can be used to indicate a possible change in momentum. If prices are falling and the RSI reaches a low and then, a few days later, it reaches a higher low (therefore, the low is not as low as the first), it indicates a possible change in momentum; we say there is a bullish divergence. Divergences are rare when a stock is in a long-term trend but is nonetheless a powerful indicator. In conclusion, the relative strength index aims to describe changes in momentum in price action through analysing and comparing previous day's highs and lows. From this, a value is generated, and at the extremes, a change in momentum may take place. RSI is not supposed to be predictive but is very helpful in confirming trends indicated by other techniques. Written by George Chant Project Gallery

Brush up on your mathematical knowledge with informative articles ranging from statistics and topology, to latent space transformations and Markov chain models. Maths Articles Brush up on your mathematical knowledge with informative articles ranging from statistics and topology, to latent space transformations and Markov chain models. You may also like: Economics , Physics , Engineering and Technology Unlocking the power of statistics What statistics are and its importance Latent spac e transformations Their hidden power in machine learning Topology In action Teaching maths How we can apply maths in our lives How to excel in maths A useful resource for students studying the subject Cognitive decision-making The maths involved Cross-curricular maths The game of life The maths behind trading A comprehensive guide to the Relative Strength Index (RSI) Markov chain models Named after the Russian mathematician, Andrei Markov, who had first studied them Proving causation Investigating why correlation doesn't necessarily mean causation, via Randomised Controlled Trials and Instrumental Variables

Maths till 18? No! All subjects till 18! Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The game of life 11/07/25, 10:03 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

Powering life and causing death Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Dual Role of Mitochondria 11/07/25, 09:57 Last updated: Published: 13/05/24, 13:38 Powering life and causing death Mitochondria as mechanisms of apoptosis Mitochondria are famous for being the “powerhouse of cells” and producing ATP for respiration by being the site for the Krebs cycle, the electron transport chain and the location of electron carriers. However, one thing mitochondria are not known for is mediating programmed cell death, or apoptosis. This is a tightly controlled process within a cell to prevent the growth of cancer cells. One way apoptosis occurs is through the mitochondria initiating protein activation in the cytosol (a part of the cytoplasm). Proteins such as cytochrome c activate caspases by binding to them, causing cell death. Caspases are enzymes that degrade cellular components so they can be removed by phagocytes. Mitochondrial apoptosis is also controlled by the B cell lymphoma 2 (BCL-2) family of proteins. They are split into pro-apoptotic and pro-survival proteins, so the correct balance of these two types of BCL-2 proteins is important in cellular life and death. Regulation and initiation of mitochondrial apoptosis Mitochondrial apoptosis can be regulated by the BCL-2 family of proteins. They can be activated due to things such as transcriptional upregulation or post-translational modification. Transcriptional upregulation is when the production of RNA from a gene is increased. Post-translational modification is when chemical groups (such as acetyl groups and methyl groups) are added to proteins after they have been translated from RNA. This can change the structure and interactions of proteins. After one of these processes, BAX and BAK (some examples of pro-apoptotic BCL-2 proteins) are activated. They form pores in the mitochondrial outer membrane in a process called mitochondrial outer membrane permeabilisation (MOMP). This allows pro-apoptotic proteins to be released into the cytosol, leading to apoptosis. Therapeutic uses of mitochondria Dysregulation of mitochondrial apoptosis can lead to many neurological and infectious diseases, such as neurodegenerative diseases and autoimmune disorders, as well as cancer. Therefore, mitochondria can act as important drug targets, providing therapeutic opportunities. Some peptides and proteins are known as mitochondriotoxins or mitocans, and they are able to trigger apoptosis. Their use has been investigated for cancer treatment. One example of a mitochondriotoxin is melittin, the main component in bee venom. This compound works by incorporating into plasma membranes and interfering with the organisation of the bilayer by forming pores, which stops membrane proteins from functioning. Drugs consisting of melittin have been used as treatments for conditions such as rheumatoid arthritis and multiple sclerosis. It has also been investigated as a potential treatment for cancer, and it induced apoptosis in certain types of leukaemia cells. This resulted in the downregulation of BCL-2 proteins, meaning there was decreased expression and activity.The result of the melittin-induced apoptosis is a preclinical finding, and more research is needed for clinical applications. This shows that mechanisms of mitochondrial apoptosis can be harnessed to create novel therapeutics for diseases such as cancer. It is evident that mitochondria are essential for respiration but also involved in apoptosis. Moreover, mitochondria are regulated by the activation of proteins like BCL-2, BAX and BAK. With further research, scientists can develop more targeted and effective drugs to treat various diseases associated with mitochondria. Written by Naoshin Haque Project Gallery

Using the new technology AI to develop drugs Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Artificial Intelligence in Drug Research and Discovery 09/07/25, 10:56 Last updated: Published: 24/05/23, 10:20 Using the new technology AI to develop drugs Drug research has been transformed by artificial intelligence (AI), which has become a game-changing technology in several industries. Only a small portion of potential drugs make it to the market after the lengthy and expensive traditional drug discovery process. A drug's discovery and development can take over ten years and cost an average of US$2.8 billion. Even then, nine out of 10 medicinal compounds fall short of passing regulatory approval and Phase II clinical trials. The use of AI in this process, however, has the potential to greatly improve effectiveness, accuracy, and success rates. Given that AI can help with rational drug design, support decision-making, identify the best course of treatment for a patient, including personalised medicines, manage the clinical data generated, and use it for future drug development, it is reasonable to assume that it will play a role in the development of pharmaceutical products from the laboratory bench to bedside table. There are several ways in which AI is currently being used to enhance the drug discovery process. One of the primary applications is virtual screening ( Figure 2 ), which involves using machine learning algorithms to analyse large libraries of chemical compounds and predict which ones are likely to be effective against a specific disease target. This can significantly reduce the time and cost required for drug discovery by narrowing down the number of compounds that need to be tested in the lab. Another way AI is being used in drug discovery is through generative models, which use deep learning algorithms to design molecules that are optimised for specific therapeutic targets. This approach can be used to design molecules that are effective against a specific target while also minimising toxicity or other undesirable properties. Data analysis is another area where AI can be applied in drug discovery. By analysing large datasets of biological and chemical information, AI can help researchers identify patterns and relationships that may be relevant to drug discovery. For example, AI can be used to analyse genomic data to identify potential drug targets or to analyse drug-drug interactions to identify potential safety issues. However, one of the main challenges is the need for high-quality data, as AI models rely on large amounts of data to make accurate predictions. Additionally, there is a risk that AI models may miss important insights or make incorrect predictions if the data used to train them is biased or incomplete. Nevertheless, the continued development of AI and its amazing tools seeks to lessen the difficulties experienced by pharmaceutical firms, impacting both the medication development process and the full lifecycle of the product, which may account for the rise in the number of start-ups in this industry. The importance of automation will increase as a result of using the most up-to-date AI-based technologies, which will not only shorten the time needed for products to reach the market but also enhance product quality, increase overall production process safety, and make better use of available resources while also being cost-effective. In conclusion, the use of AI in drug discovery has the potential to revolutionize the field and significantly improve the success rate of potential drug candidates. Despite the challenges and limitations, the continued research and development of AI in drug discovery will undoubtedly lead to faster, cheaper, and more accurate drug development. Written by Navnidhi Sharma Related articles: A breakthrough procedure in efficient drug discovery / AI in medicinal chemistry / AI advancing genetic disease diagnosis 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 12/09/25, 11:10 Last updated: Published: 07/09/24, 20:20 A rare neurological disease that is caused by a flaw in genetics This is article no. 8 in a series on Rare Diseases. Next article: Breaking down Tay-Sachs . Previous article: Apocrine carcinoma . An overview Name of the disease: Pseudo-Angelman Syndrome Other names the disease is known by: - 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 Research is ongoing for a cure, and it is considering targeting particular genes of chromosome 2 in therapy- perhaps the MBD5 and ECP2 genes. 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 (e.g. MBD5 and ECP2 ) 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 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, 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

iPSCs are one of the most powerful tools of biosciences Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The endless possibilities of iPSCs and organoids 11/07/25, 10:02 Last updated: Published: 20/01/24, 11:50 iPSCs are one of the most powerful tools of biosciences On the 8th of October 2012, the Nobel Prize in Physiology was given to Shinya Yamanaka and John B. Gurdon for a groundbreaking discovery; induced Pluripotent Stem Cells (iPSCs). The two scientists discovered that mature, specialised cells can be reprogrammed to their initial state and consequently transformed into any cell type. These cells can be used to study disease, examine genetic variations and test new treatments. The science behind iPSCs The creation of iPSCs is based on the procedure of cell potency during mammalian development. While the organism is still in the embryonic stage, the first cell developed is a totipotent stem cell, which has the unique ability to differentiate into any cell type in the human body. “Totipotent” refers to the cell’s potential to give rise to all cell types and tissues needed to develop an entire organism. As the totipotent cell grows, it develops into the pluripotent cell, which can differentiate into the three types of germ layers; the endoderm line, the mesoderm line and the ectoderm line. The cells of each line then develop into multipotent cells, which are derived into all types of human somatic cells, such as neuronal cells, blood cells, muscle cells, skin cells, etc. Creation of iPSCs and organoids iPSCs are produced through a process called cellular reprogramming, which involves the reprogramming of differentiated cells to revert to a pluripotent state, similar to that of embryonic stem cells. The process begins with selecting any type of somatic cell from the individual (in most cases, the individual is a patient). Four transcription factors, Oct4, Sox2, Klf4 and c-Myc, are introduced into the selected cells. These transcription factors are important for the maintenance of pluripotency. They are able to activate the silenced pluripotency genes of the adult somatic cells and turn off the genes associated with differentiation. The somatic cells are now transformed into iPSCs, which can differentiate into any somatic cell type if provided with the right transcription factor. Although iPSCs themselves have endless applications in biosciences, they can also be transformed into organoids, miniature three-dimensional organ models. To create organoids, iPSCs are exposed to a specific combination of signalling molecules and growth factors that mimic the development of the desired organ. Current applications of iPSCs As mentioned earlier, iPSCs can be used to study disease mechanisms, develop personalised therapies and test the action of drugs in human-derived tissues. iPSCs have already been used to model cardiomyocytes, neuronal cells, keratinocytes, melanocytes and many other types of cells. Moreover, kidney, liver, lung, stomach, intestine, and brain organoids have already been produced. In the meantime, diseases such as cardiomyopathy, Alzheimer’s disease, cystic fibrosis and blood disorders have been successfully modelled and studied with the use of iPSCs. Most importantly, the use of iPSCs in all parts of scientific research reduces or replaces the use of animal models, promising a more ethical future in biosciences. Conclusion iPSCs are one of the most powerful tools of biosciences at the moment. In combination with gene editing techniques, iPSCs give accessibility to a wide range of tissues and human disorders and open the doors for precise, personalised and innovative therapies. iPSCs not only promise accurate scientific research but also ethical studies that minimise the use of animal models and embryonic cells. Written by Matina Laskou Related articles: Organoids in drug discovery / Introduction to stem cells Project Gallery