Search Index

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The game of life 24/09/24, 13:14 Last updated: 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 Monkey see, monkey clone 06/01/25, 13:37 Last updated: A leap forward in primate research Chinese scientists have recently unlocked the secrets of cloning Rhesus monkeys offering new hope for medical breakthroughs. Introduction When we think of cloning, perhaps the first thing that comes to mind is Dolly the sheep, the first mammal ever cloned from an adult cell back in 1996. This groundbreaking achievement inspired a revolution leading to the successful cloning of other mammals such as cattles and pigs. However, cloning primates, especially Rhesus monkeys, has proven to be a significant challenge due to the low success rates and high embryonic losses during development. What is cloning? Cloning is the process of creating an identical genetic copy of an organism. In mammals, this is typically done through a technique called somatic cell nuclear transfer (SCNT). In SCNT, the nucleus (the compartment storing genetic material) from a cell of the animal to be cloned is transferred into an egg cell that has had its own nucleus removed. This hybrid egg cell then develops into an embryo which is implanted into a surrogate mother to grow into a new individual. Despite the success in cloning other mammals, cloning primates has proven to be a significant challenge. However, the potential benefits of cloning primates for medical research make it a worthwhile endeavour. The importance of cloning primates You might be wondering why being able to clone primates is so important. Well, primates like the Rhesus monkey are invaluable models for studying human diseases and create new therapies! The reason we can use them as disease models is because they share about 93% genetic identity and have very similar physiological characteristics with humans. For instance, Rhesus monkeys also experience a decline in their cognitive abilities as they age, and they lose important connections between brain cells in the part of the brain responsible for complex thinking, even when there's no severe brain damage. Moreover, Rhesus monkeys also develop the same kinds of brain changes that we see in people with Alzheimer's disease, such as the buildup of sticky proteins called amyloid-beta and tangled fibres of another protein called tau.These similarities make them excellent models for understanding how human diseases progress and for developing new treatments. So, by cloning these animals, researchers might be able to create monkeys with specific genetic changes that mimic human diseases even more closely. This could allow scientists to study these diseases in greater detail and develop more effective therapies. Cloning primates could give us a powerful tool to fight against some of the most challenging disorders that affect the human brain! A breakthrough in primate cloning Now, a group of scientists in China have made a breakthrough in primate cloning. They successfully cloned a Rhesus monkey using a novel technique called trophoblast replacement (TR).This innovative approach not only helps us better understand the complex process of cloning but also offers a promising way to improve the efficiency of primate cloning, bringing us one step closer to unlocking the full potential of this technology for medical research and beyond. The awry DNA methylation of cloned conkey embryos To understand why cloning monkeys is so challenging, Liao and colleagues (2024) took a closer look at the genetic material of embryos created in two different ways. They compared embryos made through a standard fertility treatment called intracytoplasmic sperm injection (ICSI) with those created via the cloning technique, SCNT. What they found was quite surprising! To make matters worse, the scientists also noticed that certain genes, known as imprinted genes, were not functioning properly in the SCNT embryos. Imprinted genes are a special group of genes that play a crucial role in embryo development. In a healthy embryo, only one copy of an imprinted gene (either from the mother or the father) is active, while the other copy is silenced. But in the cloned embryos, both copies were often incorrectly switched on or off. Here's the really concerning part: these genetic abnormalities were not just present in the early embryos but also in the placentas of the surrogate monkey mothers carrying the cloned offspring. This suggests that the issues arising from the cloning process start very early in development and continue to affect the pregnancy. Liao and colleagues suspect that the abnormal DNA methylation patterns might be responsible for the imprinted gene malfunction. It's like a game of genetic dominos – when one piece falls out of place, it can cause a whole cascade of problems down the line. Piecing together this complex genetic puzzle is crucial for understanding why primate cloning is so difficult and how we can improve its success in the future. By shedding light on the mysterious world of DNA methylation and imprinted genes, Liao and colleagues have brought us one step closer to unravelling the secrets behind monkey cloning. Digging deeper: what does the data reveal? Liao et al. (2024) discovered that nearly half of the cloned monkey foetuses died before day 60 of the gestation period, indicating developmental defects in the SCNT embryos during implantation. They also found that the DNA methylation level in SCNT blastocysts was 25% lower compared to those created through ICSI (30.0% vs. 39.6%). Furthermore, out of the 115 human imprinting genes they examined in both the embryos and placentas, four genes - THAP3, DNMT1, SIAH1, and RHOBTB3 - showed abnormal expression and loss of DNA methylation in SCNT embryos. These findings highlight the complex nature of the reprogramming process in SCNT and the importance of imprinted genes in embryonic development. By understanding these intricacies, scientists can develop targeted strategies to improve the efficiency of primate cloning. The power of trophoblast replacement To avoid the anomalies in SCNT placentas, the researchers developed a new method called TR. In this method, they transferred the inner cell mass (the part of the early embryo that develops into the baby) from an SCNT embryo into the hollow cavity of a normal embryo created through fertilisation, after removing its own inner cell mass. The idea behind this technique is to replace the abnormal placental cells in the SCNT embryo with healthy ones from the normal embryo. And it worked! Using this method, along with some additional treatments, Liao et al. (2024) successfully cloned a healthy male Rhesus monkey that has survived for over two years (FYI his name is Retro!). The ethics of cloning While the scientific advances in primate cloning are exciting, they also raise important ethical questions. Some people worry about the potential misuse of this technology, for instance to clone humans, which is widely considered unethical. Others are concerned about the well-being of cloned animals, as the cloning process can sometimes lead to health problems. As scientists continue to make progress in cloning technology, it is essential to have open discussions about the ethical implications of their work. Rules and guidelines must be put in place to ensure that this technology is developed and used responsibly, with the utmost care for animal welfare and the concerns of society. Looking to the future The successful cloning of a rhesus monkey using TR opens up new avenues for primate research. This technology can help scientists create genetically identical monkeys to study a wide range of human diseases, from neurodegenerative disorders like Alzheimer's and Parkinson's to infectious diseases like HIV and COVID-19. The trophoblast replacement technique developed by Liao et al. (2024) increases the likelihood of successful cloning by replacing the abnormal placental cells in the SCNT embryo with healthy ones from a normal embryo. However, it is important to note that this technique does not affect the genetic similarity between the clone and the original monkey, as the inner cell mass, which gives rise to the foetus, is still derived from the SCNT embryo. Moreover, this research provides valuable insights into the mechanisms of embryonic development and the role of imprinted genes in this process. By understanding these fundamental biological processes, scientists can not only improve the efficiency of cloning but also develop new strategies for regenerative medicine and tissue engineering. As we look to the future, cloning monkeys could help us make groundbreaking discoveries in medical research and develop new treatments for human diseases. However, we must also carefully consider the ethical implications of cloning primates and ensure that this powerful tool is used responsibly and for the benefit of society. Written by Irha Khalid Related article: Germline gene therapy (GGT) REFERENCES Beckman, D. and Morrison, J.H. (2021). Towards developing a rhesus monkey model of early Alzheimer’s disease focusing on women’s health. American Journal of Primatology , [online] 83(11). doi: https://doi.org/10.1002/ajp.23289 . Liao, Z., Zhang, J., Sun, S., Li, Y., Xu, Y., Li, C., Cao, J., Nie, Y., Niu, Z., Liu, J., Lu, F., Liu, Z. and Sun, Q. (2024). Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer. Nature Communications , [online] 15(1), p.5. doi: https://doi.org/10.1038/s41467-023-43985-7 . Morrison, J.H. and Baxter, M.G. (2012). The ageing cortical synapse: hallmarks and implications for cognitive decline. Nature Reviews Neuroscience , [online] 13(4), pp.240–250. doi: https://doi.org/10.1038/nrn3200 . Paspalas, C.D., Carlyle, B.C., Leslie, S., Preuss, T.M., Crimins, J.L., Huttner, A.J., Dyck, C.H., Rosene, D.L., Nairn, A.C. and Arnsten, A.F.T. (2017). The aged rhesus macaque manifests Braak stage III/IV Alzheimer’s‐like pathology. Alzheimer’s & Dementia , [online] 14(5), pp.680–691. doi: https://doi.org/10.1016/j.jalz.2017.11.005 . Shi, L., Luo, X., Jiang, J., Chen, Y., Liu, C., Hu, T., Li, M., Lin, Q., Li, Y., Huang, J., Wang, H., Niu, Y., Shi, Y., Styner, M., Wang, J., Lu, Y., Sun, X., Yu, H., Ji, W. and Su, B. (2019). Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development. National Science Review , [online] 6(3), pp.480–493. doi: https://doi.org/10.1093/nsr/nwz043 . Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The environmental impact of EVs 16/01/25, 11:21 Last updated: A chemical perspective Electric vehicles (EVs) are gaining momentum worldwide as a greener alternative to conventional internal combustion engine vehicles (ICEVs). The environmental benefits of EVs extend beyond their efficient use of electricity. In this article, we explore the chemical aspects of EVs and their environmental impact, shedding light on their potential to mitigate climate change and reduce pollution. Greenhouse Gas Emissions Reduction: EVs play a crucial role in addressing climate change by significantly reducing greenhouse gas (GHG) emissions. Unlike ICEVs that rely on fossil fuels, EVs generate zero tailpipe emissions. By utilising electricity as their energy source, EVs minimise the release of carbon dioxide (CO2) and other GHGs responsible for global warming. However, it's essential to consider the environmental implications of electricity generation, emphasising the need for renewable energy sources to maximise the positive impact of EVs. Battery Chemistry and Resource Management: The heart of an EV lies in its rechargeable battery, typically composed of lithium-ion technology. The production and disposal of these batteries present both opportunities and challenges. Raw materials, such as lithium, cobalt, and nickel, are essential components of EV batteries. Responsible mining practices and efficient recycling techniques are vital to minimising the environmental impact of resource extraction and ensuring proper disposal or repurposing of used batteries. Electrochemical Reactions and Energy Storage: Electric vehicles rely on electrochemical reactions within their batteries to store and release energy. These reactions involve the flow of ions, typically lithium ions, between the positive and negative electrodes. Understanding the chemistry behind these processes enables the development of more efficient and durable battery systems. Continued research and innovation in battery chemistry hold the potential to enhance energy storage capabilities, extend EV range, and improve overall performance. Air Quality and Emission Reduction: EVs contribute to improved air quality due to their zero tailpipe emissions. By eliminating the release of pollutants such as nitrogen oxides (NOx), particulate matter (PM), and volatile organic compounds (VOCs), EVs reduce smog formation and respiratory health risks. This is particularly significant in urban areas, where high concentrations of vehicular emissions contribute to air pollution. The adoption of EVs can help combat these issues and create cleaner and healthier environments. Battery Recycling and the Circular Economy: Given the increasing demand for EVs, battery recycling plays a vital role in ensuring a sustainable future. Recycling allows for the recovery of valuable materials and reduces the need for resource extraction. Effective recycling processes can mitigate the environmental impact of battery production, minimise waste generation, and promote a circular economy approach, where materials are reused and recycled to their fullest extent. Future Prospects and Chemical Innovations : Advancements in battery technology and chemical engineering are key to unlocking the full potential of EVs. Research efforts are focused on developing alternative battery chemistries, such as solid-state batteries, which offer improved energy density, safety, and recyclability. Additionally, exploring sustainable materials and manufacturing processes for batteries can further reduce the environmental footprint of EVs. In conclusion, electric vehicles represent a promising solution to combat climate change, reduce pollution, and promote sustainable transportation. From the chemistry behind battery systems to their impact on air quality and resource management, EVs offer a greener alternative to traditional vehicles. Continued research, innovation, and collaboration between the automotive industry, chemical scientists, and policymakers are essential for realising the full potential of EVs and creating a cleaner, more sustainable future. Written by Navnidhi Sharma Related articles: Hydrogen cars / The brain-climate connection / Plastics and their environmental impact Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A common diabetes drug treating Parkinson’s disease 24/04/24, 10:14 Last updated: Treating this brain disorder with a diabetic 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? Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Sideroblastic anaemia 06/01/25, 13:36 Last updated: 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 article: Blood Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring Ibuprofen 24/09/24, 11:00 Last updated: Its toxicodynamics, and balancing benefits and risks What is Ibuprofen? Ibuprofen is a standard over-the-counter medicine which can be bought from supermarkets and pharmacies. It is primarily used for pain relief, such as back pain, period pain, toothaches, etc. It can also be used for arthritis pain and inflammation. It is available in various forms, including tablets, capsules, gels, and sprays for the skin. The Toxicodynamics of Ibuprofen Toxicodynamics refers to the biological effects of a substance after exposure to it. Scientists look at the mechanisms by which the substance produces toxic effects and the target organs or tissues it affects. Ibuprofen works by stopping the enzymes that synthesise prostaglandins, which are a group of lipid molecules that cause inflammation, including symptoms like redness, heat, swelling and pain. Therefore, after the action of Ibuprofen, inflammatory responses and pain are reduced. Ibuprofen targets organs and tissues, including the gastrointestinal tract, the kidneys, the central nervous system, blood and more. Balancing the Benefits and Risks Ibuprofen’s method of action means it is a safe and effective pain relief medication for most people. It is also easily accessible and easy to use. However, it is able to affect the target organs and tissues negatively and, therefore, can have serious side effects, especially if taken for an extended period of time and/or in high doses. They include heartburn, abdominal pain, kidney damage (especially for people who already have kidney problems), low blood count and more. Therefore, it is important to use Ibuprofen responsibly. This can be done by understanding and being well-informed about its effects on the body, particularly its impact on organs and tissues. With caution and proper use, the side effects can be minimised. One of the easiest ways to lessen side effects is by taking the medication with food. Additionally, patients should take the lowest effective dose for the shortest possible time. If patients have a history of stomach problems, avoiding Ibuprofen and using alternatives is the best solution. Patients can also talk to their GP if they are concerned about the side effects and report any suspected side effects using the Yellow Card safety scheme on the NHS website. Links to find out more: https://www.nhs.uk/medicines/ibuprofen-for-adults/about-ibuprofen-for-adults/ https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/toxicodynamics https://www.chm.bris.ac.uk/motm/ibuprofen/ibuprofenh.htm https://www.ncbi.nlm.nih.gov/books/NBK526078/ Written by Naoshin Haque Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Story of the atom 20/04/24, 11:16 Last updated: 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

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Topology in action 24/09/24, 13:21 Last updated: Properties of space Let’s say I put a sphere in front of you. I’m sure you could go through and tell me the basic facts and formulas surrounding it, many if which containing Pi. And even better, if you were a bit more fluent in maths, you could go further and start telling me about the geometry of the shape, say how the gradient had to disappear at a certain point or an assortment of many other things. But if we dive a little deeper into pure maths, it starts getting a little more complicated. When labels like Hausdorff get casually thrown about (meaning you can always separate two distinct points with an open boundary, which you certainly can do on a sphere!) it can really build up and become quite hard, especially if someone then puts in front of you two spheres stuck together. This is where the study of topology comes in and starts helping out, allowing us to start to categorise certain spaces without having to worry about all the small details that could catch you out. Topology is certainly found in the purer side of maths, generally seen as one of the more abstract modules to be taking at undergraduate level (as seen by the exam scores). But thinking of it just as some far away concept disconnected with the rest of the world would be foolish. Thinking back to what I said before about gradient fields on a sphere, this is more commonly known in maths as the “Hairy Ball Theorem” named as such as if you had a ball of hair, you wouldn’t be able to smooth it all out without a cow’s lick. And in mathematical terms it means that a continuous vector field has to disappear at a certain point. And maybe not readily apparent but this comes up in loads of places, the most obvious of which is that two points on the Earth will always have the exact temperature! But moving to Biology we see a lot more applications, even as early as in A-level study. Just thinking about how a protein will fold is all to do with the topological properties of them. DNA is a bit more complex understandably, with more base pairs it becomes incredibly flexible, able to bend into many shapes, but like topological spaces this flexible has limits. It doesn’t pass through itself nor tear, so it allows us to start applying our theorems to it. A key one of these is Knot theory, which of course is the study of knots. Knots in maths are defined as having no open ends and being complex, which helpfully is exactly like DNA! As you hopefully know, its coiled form has no open ends, and in order to untangle it we have to go through the process of cutting at double points. The amount of times this is needed to untangle is called the unknotting number in topology and this mathematical modelling of the process allows biologists to move away from the microscope and still get a more accurate look on what’s happening. Written by Tom Murphy Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Brief neuroanatomy of autism 10/10/24, 10:28 Last updated: Differences in brain structure Autism is a neurodevelopmental condition present in both children and adults worldwide. The core symptoms include difficulties understanding social interaction and communication, and restrictive or repetitive behaviours such as strict routines and stimming. When the term autism was first coined in the 20th century, it was thought of as a disease. However, it is now described as a cognitive difference rather than a disease; that is, the brains of autistic individuals – along with people diagnosed with dyslexia, dyspraxia, or attention deficit hyperactive disorder – are not defective, but simply wired differently. The exact cause or mechanism for autism has not been determined; the symptoms are thought to be brought about by a combination of genetic and environmental factors. Currently, autism disorders are diagnosed solely by observing behaviours, without measuring the brain directly. However, behaviours may be seen as the observable consequence of brain activity. So, what is it about their brains that might make autistic individuals behave differently to neurotypicals? Total brain volume Back before sophisticated imaging techniques were in use, psychiatrics had already observed the head size of autistic infants was often larger than that of other children. Later studies provided more evidence that most children who would go on to be diagnosed had a normal-sized head at birth, but an abnormally large circumference by the time they had turned 2 to 4 years old. Interestingly, increase in head size has been found to be correlated with the onset of main symptoms of autism. However, after childhood, growth appears to slow down, and autistic teenagers and adults present brain sizes comparable to those of neurotypicals. The amygdala As well transient increase of total brain volume, the size and volume of several brain structures in particular seems to differ between individuals with and without autism. Most studies have found that the amygdala, a small area in the centre of the brain that mediates emotions such as fear, appears enlarged in autistic children. The amygdala is a particularly interesting structure to study in autism, as individuals often have difficulty interpreting and regulating emotions and social interactions. Its increased size seems to persist at least until early adolescence. However, studies in adolescents and adults tend to show that the enlargement slows down, and in some cases is even reversed so that the number of amygdala neurons may be lower than normal in autistic adults. The cerebellum Another brain structure that tends to present abnormalities in autism is the cerebellum. Sitting at the back of the head near the spinal cord, it is known to mediate fine motor control and proprioception. Yet, recent literature suggests it may also play an important role in some higher other cognitive functions, including language and social cognition. Specifically, it may be involved in our ability to imagine hypothetical scenarios and to abstract information from social interactions. In other words, it may help us recognise similarities and patterns in past social interactions that we can apply to understand a current situation. This ability is poor in autism; indeed, some investigations have found the volume of the cerebellum may be smaller in autistic individuals, although research is not conclusive. Nevertheless, most research agrees that the number of Purkinje cells is markedly lower in people with autism. Purkinje cells are a type of neuron found exclusively in the cerebellum, able to integrate large amounts of input information into a coherent signal. They are also the only source of output for the cerebellum; they are responsible for connecting the structure with other parts of the brain such as the cortex and subcortical structures. These connections eventually bring about a specific function, including motor control and cognition. Therefore, a low number of Purkinje cells may cause underconnectivity between the cerebellum and other areas, which might be the reason for functions such as social cognition being impaired in autism. Written by Julia Ruiz Rua Related article: Epilepsy Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Germline gene therapy (GGT): its potential and problems 06/01/25, 13:38 Last updated: A Scientia News Biology and Genetics collaboration Introduction Genetic diseases arise when there are alterations or mutations to genes or genomes. In most acquired cases, mutations occur in somatic cells. However, when these mutations happen in germline cells (i.e. sperm and egg cells), they are incorporated into the genome of every cell. In other words, should this mutation be deleterious, all cells will have this issue. Furthermore, this mutation becomes inheritable. This is partly why most genetic diseases are complicated to treat and cure. Gene therapy is a concept that has been circulating among geneticists for some time. Indeed, addressing a disease directly from the genes that caused or promoted it has been an attractive and appealing avenue of therapies. The first successful attempt at gene therapy dates back to 1990, using retrovirus-derived vectors to transduce the T-lymphocytes of a 4-year-old girl with X-linked severe combined immunodeficiency disease (SCID-X1) with enzyme adenosine deaminase (ADA) deficiency. The trial was a great success, eliminating the girl's disease and marking a great milestone in the history of genetics. Furthermore, the success of viral vectors also opened new avenues to gene editing, such as zinc finger nucleases and the very prominent CRISPR-Cas9. For example, in mid-November 2023, the UK Medicines and Healthcare products Regulatory Agency or MHRA approved the CRISPR-based gene therapy, Casgevy, for sickle cell disease and β-thalassemia. It is clear that the advent of gene therapies significantly shaped the treatment landscape and our approach to genetic disorders. However, for most of gene therapy history, it is done almost exclusively on somatic cells or some stem cells, not germline cells. How it works As mentioned, inherited genetic disease-associated mutations are also present in germline cells or gametes. The current approach to gene therapy targets genes of some or very specific somatic or multipotent stem cells. For example, in the 1990 trial, the ADA-deficient SCID-X1 T-lymphocytes were targeted, and in recently approved Casgevy, the BCL11A erythroid-specific enhancer in hematopoietic stem cells. The methods involved in gene therapies also vary, each with advantages and limitations and carrying some therapeutic risks. Nevertheless, when aiming to treat genetic diseases, gene therapy should answer two things: how to do it and where. There are a few elucidated strategies of gene therapies. Unlike some popular beliefs, gene therapies do not always directly change or edit mutated genes. Instead, some gene therapies target enhancers or regulatory regions that control the expression of mutated genes. In other cases, such as in Casgevy, enhancers of a different subtype are targeted. By targeting or reducing BCL11A expression, Casgevy aims to induce the production of foetal haemoglobin (HbF), which contains the γ-globin chain as opposed to the defective β-chain in the adult haemoglobin (HbA) of sickle cell disease or β-thalassemia. Some gene therapies can also be done ex vivo or in vivo . Ex vivo strategies involve extracting cells from the body and modifying them in the lab, whilst in vivo strategies directly modify the cell without extraction (e.g. using viral/ non-viral vectors to insert genes). In essence, the list of strategies for gene therapies is growing, each with limitations and a promising prospect of tackling genetic diseases. These methods aim to “cure” genetic diseases in patients. However, the strategies mentioned above have all been researched using and, perhaps, made therapeutically for somatic or multipotent stem cells. Germline gene therapy (GGT), involves directly editing the genetic materials of germline cells or the egg and sperm cells before fertilisation. This means if it is done successfully, fertilisation of these cells will eliminate the disease phenotype from all cells of the offspring instead of only effector cells. Potentially, GGT may eradicate a genetic disease for all future generations. Therefore, it is an appealing alternative to human embryo editing, as it achieves similar or the same result without the need to modify an embryo. However, due to its nature, its advantage may also be its limitation. Ethical issues GGT has the potential to cure genetic disorders within families. However, because it involves editing either the egg or sperm cells before fertilisation, there are prominent ethical issues associated with this method, like the use of embryos for research and many more. Firstly, GGT gives no room for error. Mistakes during the gene modification process could cause systemic side effects or a harsher disease than the one initially targeted, leading to a multigenerational effect. For example, if parents went to a clinic to check if one/both their germ cells have a gene coding for proteins implicated in cystic fibrosis, an off-target mistake during GGT may lead to their child developing Prader-Willi Syndrome or other hereditary disorders caused by editing out significant genes for development. Secondly, an ecological perspective asserts that the current human gene pool, an outcome of many generations of natural selection, could be weakened by germline gene editing. Also, there is the religious perspective, where editing embryos goes against the natural order of how god created living creatures as they should be, where their natural phenotypes are “assigned” for when they are alive. Another reason GGT may be unethical is it leads to eugenics or creating “designer babies”. These are controversial ideas dating back to the late 19th century, where certain traits are “better” than others. This implies they should appear in human populations while individuals without them should be sterilised/killed off. For instance, it is inconceivable to forget the Nazi Aktion T4 program, which sought to murder disabled people because they were seen as “less suitable” for society. Legal and social issues Eugenics is notorious today because of its history. Genetic counselling may be seen like this as one possible outcome may be parents who end pregnancies if their child inherits a genetic disease. Moreover, understanding GGT’s societal influences is crucial, so clinical trial designs must consider privacy, self-ownership, informed consent and social justice. In China, the public’s emotional response to GGT in 2018 was mainly neutral, as shown in Figure 1, but some of the common “hot words” when discussed were ‘mankind’, ‘ethics’, and ‘law’. With this said, regulations are required with other nations for a wider social consensus on GGT research. In other countries, there are stricter rules for GGT. it is harder to conduct experiments using purposely formed/altered human embryos with inheritable mutations in the United States because the legal outcomes can include prison time and $100,000 fines. Furthermore, when donors are required, they must be fairly compensated, and discussing methodologies is crucial because there are issues on how they can impact men and women. South Africa has two opposing thoughts on GGT or gene editing. Bioconservatism has worries about genetic modification and asserts its restrictions, while bioliberalism is receptive to this technology because of the possible benefits. Likewise, revisions to the current regulations are suggested, such as rethinking GGT research or a benefit-risk analysis for the forthcoming human. Conclusion Overall, gene therapies have transformed the therapeutic landscape for genetic diseases. GGT is nevertheless a unique approach that promises to completely cure a genetic disease for families without the need to edit human embryos. However, GGT’s prospects may do more harm than good because its therapeutic effects are translated systemically and multigenerationally. On top of that, controversial ideas such as designer babies can arise if GGT is pushed too far. Additionally, certain countries have varying regulations due to cultural attitudes towards particular scientific innovations and the beginning of life. Reflecting on the ethical, legal and social issues, GGT is still contentious and probably would not be a prominent treatment option anytime soon for genetic diseases. Written by Sam Jarada and Stephanus Steven Introduction, and How it works by Stephanus Ethical issues, and Legal and social issues by Sam Conclusion by Sam and Stephanus Related article: Monkey see, monkey clone References: Cavazzana-Calvo, M. et al. (2000) ‘Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease’, Science , 288(5466), pp. 669–672. doi:10.1126/science.288.5466.669. Demarest, T.G. and Biferi, M.G. (2022) ‘Translation of gene therapy strategies for amyotrophic lateral sclerosis’, Trends in Molecular Medicine , 28(9), pp. 795–796. doi:10.1016/j.molmed.2022.07.001. Frangoul, H. et al. (2021) ‘CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia’, New England Journal of Medicine , 384(3), pp. 252–260. doi:10.1056/nejmoa2031054. AGAR, N. (2018). Why We Should Defend Gene Editing as Eugenics. Cambridge Quarterly of Healthcare Ethics, 28(1), pp.9–19. doi: https://doi.org/10.1017/s0963180118000336 . de Miguel Beriain, I., Payán Ellacuria, E. and Sanz, B. (2023). Germline Gene Editing: The Gender Issues. Cambridge Quarterly of Healthcare Ethics, 32(2), pp.1–7. doi: https://doi.org/10.1017/s0963180122000639 . Genome.gov . (2021). Eugenics: Its Origin and Development (1883 - Present). [online] Available at: https://www.genome.gov/about-genomics/educational-resources/timelines/eugenics#:~:text=Discussions%20of%20eugenics%20began%20in . Johnston, J. (2020). Budgets versus Bans: How U.S. Law Restricts Germline Gene Editing. Hastings Center Report, 50(2), pp.4–5. doi: https://doi.org/10.1002/hast.1094 . Kozaric, A., Mehinovic, L., Stomornjak-Vukadin, M., Kurtovic-Basic, I., Catibusic, F., Kozaric, M., Mesihovic-Dinarevic, S., Hasanhodzic, M. and Glamuzina, D. (2016). Diagnostics of common microdeletion syndromes using fluorescence in situ hybridization: single center experience in a developing country. Bosnian Journal of Basic Medical Sciences, [online] 16(2). doi: https://doi.org/10.17305/bjbms.2016.994 . Luque Bernal, R.M. and Buitrago BejaranoR.J. (2018). Assessoria genética: uma prática que estimula a eugenia? Revista Ciencias de la Salud, 16(1), p.10. doi: https://doi.org/10.12804/revistas.urosario.edu.co/revsalud/a.6475 . Nielsen, T.O. (1997). Human Germline Gene Therapy. McGill Journal of Medicine, 3(2). doi: https://doi.org/10.26443/mjm.v3i2.546 . Niemiec, E. and Howard, H.C. (2020). Germline Genome Editing Research: What Are Gamete Donors (Not) Informed About in Consent Forms? The CRISPR Journal, 3(1), pp.52–63. doi: https://doi.org/10.1089/crispr.2019.0043 . Peng, Y., Lv, J., Ding, L., Gong, X. and Zhou, Q. (2022). Responsible governance of human germline genome editing in China. Biology of Reproduction, 107(1). doi: https://doi.org/10.1093/biolre/ioac114 . Shozi, B. (2020). A critical review of the ethical and legal issues in human germline gene editing: Considering human rights and a call for an African perspective. South African Journal of Bioethics and Law, 13(1), p.62. doi: https://doi.org/10.7196/sajbl.2020.v13i1.00709 . Thaldar, D., Botes, M., Shozi, B., Townsend, B. and Kinderlerer, J. (2020). Human germline editing: Legal-ethical guidelines for South Africa. South African Journal of Science, 116(9/10). doi: https://doi.org/10.17159/sajs.2020/6760 . Zhang, D. and Lie, R.K. (2018). Ethical issues in human germline gene editing: a perspective from China. Monash Bioethics Review, 36(1-4), pp.23–35. doi: https://doi.org/10.1007/s40592-018-0091-0 . Project Gallery