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Code to cure Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link How did bioinformatics allow for swift development of the SARS-CoV-2 vaccine? 30/01/25, 12:36 Last updated: Published: 03/09/24, 13:05 Code to cure Traditionally, vaccine development takes years. However, the urgent need for a vaccine to mitigate the effects of this pandemic sped up the process. Bioinformaticians played a crucial role in enabling the swift development of effective SARS-CoV-2 vaccines in many ways. Bioinformatics is the science of performing computational analysis and applying computational tools to capture and interpret biological data. The SARS-CoV-2 virus, with its rapid transmission and mutation rates, quickly became one of the most widespread and economically disruptive pandemics in history. According to Naseer et al. (2022), the global economy has been estimated to lose nearly 9 trillion due to the pandemic by the chief of the International Monetary Fund (IMF). Scientists sequenced the SARS-CoV-2 virus within the first few months of the viral outbreak, and the first SARS-CoV-2 genome sequence was published on GenBank on 10 January 2020. However, a sequence on its own means little, that is until the genes and regulatory elements present in the genome are determined. This was made possible by many bioinformatic tools and pipelines such as: - BLAST (Basic Local Alignment Search Tool): A sequence alignment tool used to find on regions of similarity and infer function and evolutionary relationships. - VADR (Viral Annotation DefineR): An automated annotation tool specifically for viral genomes - Velvet: A de novo sequence assembler i.e. it constructs a longer, full sequence from short read data obtained from next-generation sequencing. The information collected by different labs was shared worldwide, which allowed for a global collaborative effort towards developing a SARS-CoV-2 vaccine. Bioinformaticians also played a role in predicting the 3D structures of the proteins on the surface of the SARS-CoV-2 virus including the spike protein, which is protein against which vaccines build immunity. By using computational tools such as AlphaFold, they could model the structure of the spike protein and identify key sites to target in immunisation strategies. Another method used to identify key sites to target is Epitope Mapping, which is the identification of specific regions on an antigen that are recognised by parts of the immune system such as T Cell Receptors and antibodies. Tools such as IEDB Analysis Resource and BepiPred allow for the identification of epitopes on the SARS-CoV-2 spike that are highly immunogenic, meaning they are able to stimulate a strong immune response, and are therefore ideal targets for vaccines. SARS-CoV-2 is a highly mutagenic virus and one incredibly important bioinformatic platform known as GISAID which has enabled the real-time monitoring of these mutations. This comprehensive and open-access database was key to updating vaccine formulations and maintaining efficacy against emerging variants. In conclusion, although sometimes overlooked, bioinformatics played a crucial factor in fighting SARS-CoV-2 as efficiently and quickly as we did. From genome sequencing to mutation mapping, bioinformaticians have taken arms at every stage of battling the SARS-CoV-2 pandemic. Written by Devanshi Shah Related articles: Origins of COVID / COVID-19 glossary / Correlation between HDI and mortality rate during the pandemic / mRNA vaccines REFERENCES Chatterjee, R., Ghosh, M., Sahoo, S., Padhi, S., Misra, N., Raina, V., Suar, M. & Son, Y.-O. (2021) Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development—A Perspective Review. Vaccines . 9 (8), 812. doi: 10.3390/vaccines9080812 . Hufsky, F., Lamkiewicz, K., Almeida, A., Aouacheria, A., Arighi, C., et al. (2020) Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research. Briefings in Bioinformatics . 22 (2), 642–663. doi: 10.1093/bib/bbaa232 . Ma, L., Li, H., Lan, J., Hao, X., Liu, H., Wang, X. & Huang, Y. (2021) Comprehensive analyses of bioinformatics applications in the fight against COVID-19 pandemic. Computational Biology and Chemistry . 95, 107599. doi: 10.1016/j.compbiolchem.2021.107599 . Torrington, E. (2022) Bioinformaticians: the Hidden Heroes of the COVID-19 Pandemic. BioTechniques . 72 (5), 171–174. doi: 10.2144/btn-2022-0039 . PYMOL: Schrödinger, LLC. (2024). PyMOL Molecular Graphics System (Version 2.5.4) [Software]. Available at: https://pymol.org/2/ [Accessed 3 Jul. 2024]. RCSB PDB 7T3M: Protein Data Bank. (2024). PDB ID: 7T3M, [online] Available at: https://www.rcsb.org/structure/7T3M [Accessed 3 Jul. 2024]. Project Gallery

Its toxicodynamics, and balancing benefits and risks Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring Ibuprofen 18/09/25, 08:47 Last updated: Published: 17/01/24, 01:28 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. Written by Naoshin Haque Related articles: Anthrax toxin / The Pain Gate Theory Project Gallery

Investigating the outbreak in Devon, UK in May 2024 Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Cryptosporidium: bridging local outbreaks to global health disparities 20/03/25, 12:06 Last updated: Published: 01/09/24, 12:50 Investigating the outbreak in Devon, UK in May 2024 In early May, news emerged of numerous Devon (UK) residents experiencing vomiting and diarrhoea. Majorly affecting the Brixham region, over 40 people were diagnosed with cryptosporidiosis, and over 16,000 homes were advised to boil water before consuming it to kill potential pathogens ( Figure 1 ). Despite a controversial handling of the situation from South West Water (SWW) (from initial denial of the ‘crisis’, to major profit increases for the company), the outbreak was eventually linked to a broken pipe from where animal faeces could have entered, contaminating the water supply, a SWW representative suggested. In this article, we will investigate the disease and its relevance worldwide. So, what is Cryptosporidiosis? Cryptosporidiosis is commonly associated with gastrointestinal symptoms, such as vomiting, diarrhoea and severe abdominal cramps. It is caused by cryptosporidium, from the Apicocomplexa family. This microorganism is an intra-cellular gut parasite which invades the microvilli in the gut and depletes host nutrients. The parasite is spread via faecal-oral transmission, and it is commonly found in contaminated water, food and animals. Its life cycle starts with oocyst (egg) ingestion, leading to attachment to host gut epithelia, and asexual reproduction. This allows sexual reproduction to ensue, and oocyst formation. Eventually, the oocysts are released via faeces, for the cycle of infection to continue. Cryptosporidium species are often identified by the immune system via Toll-Like Receptors, specifically TLR-4, in the gut epithelia; Cryptosporidium-derived molecules are treated as TLR-4 ligands, since the microbe does not produce LPS molecules. Adaptive immune signalling pathways, such as NF-kB, are triggered, encouraging IL-8, CXCL1 and other chemokine secretion from the gut ( Figure 2 ). Consequently, gut inflammation is increased, as well as levels of Intracellular Adhesion Molecule-1 (ICAM-1), to aid immunocyte recruitment and improve pathogenic clearance. Other mechanisms the epithelial barrier uses to eliminate cryptosporidium infection include NO secretion and mucin production, to kill the pathogen, and prevent further infection by blocking extracellular oocyst binding, respectively. In some individuals, cryptosporidium can evade immune response due to its intracellular nature. Most immunocompetent patients suffer mild symptoms and so are offered symptomatic treatment, but some immunocompromised patients (those with HIV, for example) can develop chronic diarrhoea as a result of cryptosporidium infection. In this instance, managing fluid loss and rest is often insufficient; these patients are prescribed nitazoxanide, a broad-spectrum antiparasitic, to manage their diarrhoea. Cryptosporidiosis on a global scale Although controversial, the management of the cryptosporidium ‘crisis’ in Devon was resolved relatively quickly compared to outbreaks in other countries ( Figure 3 ). There are clear links between socio-economic dynamics and water-borne illness prevalence. In some developing regions, such as areas in the Middle East and North Africa (MENA), cryptosporidiosis is considered endemic, due to poor quality water-sanitation centres, rapid population growth and inadequate potable water supply. Globally, 3.4 million people die each year from water-borne illnesses - and poor sanitation ranks higher in causes of human morbidity than war and terrorism. Additionally, in 2015, cryptosporidium was the fourth leading cause of death amongst children under 5, clearly highlighting the danger this parasite can cause. For children in developing countries, who are already predisposed to starvation, cryptosporidiosis can kick-start a malnutrition cycle. Here, cryptosporidium exacerbates host malnutrition due to its parasitic nature, potentially causing cognitive impairment and growth stunting. Cryptosporidiosis, although typically mild, can be devastating for some people (the immunocompromised and young children). Particularly, those who are malnourished can suffer severe effects. The water contamination in Devon (UK), handled by SWW, was unfortunate and many in the region experienced severe illness. Globally, cryptosporidiosis is a major problem and in some regions, it is considered endemic. Thus, it is important we spread awareness of the devastating effects of this disease, continue efforts to prevent transmission and strive for eradication. Written by Eloise Nelson REFERENCES Abuseir, S. (2023) ‘A systematic review of frequency and geographic distribution of water-borne parasites in the Middle East and North Africa’, Eastern Mediterranean Health Journal , 29(2), pp. 151–161. doi:10.26719/emhj.23.016. Chalmers, R.M., Davies, A.P. and Tyler, K. (2019) ‘Cryptosporidium’, Microbiology , 165(5), pp. 500–502. doi:10.1099/mic.0.000764. Hassan, E.M. et al. (2020) ‘A review of cryptosporidium spp. and their detection in water’, Water Science and Technology , 83(1), pp. 1–25. doi:10.2166/wst.2020.515. News, S. (2024) ‘Brixham: More than 50 people in Devon ill from contaminated water - as South West Water’s owner posts £166m profit’, Sky News , 21 May. Available at: https://news.sky.com/story/brixham-more-than-50-people-in-devon-ill-from-contaminated-water-as-south-west-waters-owner-posts-166m-profit-13140820#:~:text=More%20than%2050%20cases%20of,water%2C%20health%20bosses%20have%20said . Sparks, H. et al. (2015) ‘Treatment of cryptosporidium: What we know, gaps, and the way forward’, Current Tropical Medicine Reports , 2(3), pp. 181–187. doi:10.1007/s40475-015-0056-9. Caccio SM. Cryptosporidium : parasite and disease, Immunology of Cryptosporidiosis. Springer Verlag Gmbh; 2016. Project Gallery

A glimpse into the early universe Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Dark Energy Spectroscopic Instrument (DESI) 23/10/25, 10:22 Last updated: Published: 08/07/23, 13:11 A glimpse into the early universe June 2023 marked the early release of data from the Dark Energy Spectroscopic Instrument (DESI). This instrument will study the nature of Dark Energy, an elusive addition to our cosmological equations that is thought to explain the accelerating expansion of the Universe. Current models estimate that Dark Energy comprises 68% of the total mass and energy of the universe and is distinct from matter and radiation in the sense that as space expands, its energy density remains constant rather than diluting. Imagine your favourite concentrated juice drink tasting the same regardless of how much water you add! DESI will investigate the large-scale structure of the Universe, obtaining spectra of around 40 million galaxies and using their redshift to create 3-D distance maps. The five-year observation effort has aptly been dubbed an experiment in “cosmic cartography”. (Redshift is the phenomenon wherein the light from objects moving away from us is stretched to longer and redder wavelengths.) The revolutionary engineering behind this instrument enables the measurement of light from more than 100,000 galaxies in a single night! This includes 5,000 optical fibres, each connected to a robotic positioner programmed to aim at galaxies from a specified target list. The survey is conducted on the 4-metre Mayall Telescope at the Kitt Peak National Observatory in Arizona. Another staggering feature DESI boasts is that the eventual sample size will outstrip the 20-year Sloan Digital Sky Survey by a factor of 10 in extra-galactic targets! The early release contains 80 Terabytes of data, representing 2% of the total dataset that should be available in 2026. See Figures 1 and 2. In 2005, the Sloan Digital Sky Survey found a signal that DESI will validate and make more precise. This signal is that of Baryonic Acoustic Oscillations (BAO). In the incredibly early universe, there were protons and neutrons, known as baryons, which existed in a hot, dense plasma with electrons. Photons were trapped in this plasma due to the extremely high probability of colliding with an electron. The universe was opaque. Only when the universe had cooled sufficiently so that protons and electrons could form neutral hydrogen atoms—an epoch known as recombination*—*did photons decouple from matter. The Cosmic Microwave Background is actually caused by these photons that were emitted after recombination. Before photons decoupled, the gravitational and high-pressure interactions in the plasma produced oscillations that radiated spherically outward from overdense regions, causing photons and baryons to travel through space together. However, as mentioned earlier, when the universe cooled and photons decoupled, the baryonic matter that was present in these oscillations became essentially frozen in space. The photons were free to stream throughout the now-transparent universe. This provided a so-called standard ruler, the distance that these baryons had travelled as an acoustic oscillation prior to recombination. Linking this back to Dark Energy requires the important detail that the radius of the spherical shell of baryons is tied to the expansion rate of the universe. As Dark Energy has propelled the Universe to expand, this standard ruler has expanded with it. See Figure 3. DESI's 3-D map of galaxies will provide a much clearer picture of the universe's large-scale structure, which is our only hope of finding the imprint of BAO. DESI will show (and has already shown) that there exists an overabundance of galaxies separated by a distance equivalent to the length of the standard ruler. Today, the size of this standard ruler is thought to be approximately 490 million lightyears. DESI represents an impressive step into the era of precision cosmology, and it will require the efforts of hundreds of scientists to make sense of the vast quantities of data we expect by 2026. Written by Joseph Brennan Related articles: Light Project Gallery

Captive breeding has grown the California condor population over 18-fold Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Conserving the California condors 24/04/25, 11:46 Last updated: Published: 04/11/24, 14:56 Captive breeding has grown the California condor population over 18-fold This is article no. 2 in a series on animal conservation. Next article: Beavers are back in Britain . Previous article: The cost of coats: celebrating 55 years of vicuna conservation . California condors are critically endangered birds living on the west coast of North America. Their population decline was first reported in 1953, and they were nearly extinct by 1987. Since then, a captive breeding and reintroduction program has saved the species in the face of multiple human threats. This article will describe some of those threats and available measures to mitigate them. Why California condors became endangered Lead poisoning was the main cause of California condor mortality in the late 20th century. Like vultures, California condors eat dead mammals. When these mammals were shot dead with lead bullets, condors ingested fragments of the bullets, and the lead poisoned their bloodstream. Multiple condors feeding on the same carcass got poisoned, which could be why the population crashed so badly. Today, lead poisoning is the biggest, but not the only, threat to California condor survival ( Figure 1 ). The birds used to be hunted for museums and private collections in the early 20th century, but nowadays, any shootings are accidental. A bigger concern, and the second-most common human-related cause of mortality, is condors colliding with utility poles and power lines. The third-most common is fires: a 2015 study found that every recent wildfire in California has coincided with at least one condor death. Climate change will make these fires more frequent and severe. These threats mainly apply to inland California condors - halogenated organic compound (HOC) pollution is an issue for coastal birds. When coastal condors eat marine mammals contaminated with HOCs, the compounds disrupt their reproductive system and thin their eggshells. In short, humans have created a hostile environment for California condors. Successful captive breeding and population recovery Despite these threats, captive breeding has grown the California condor population over 18-fold ( Figure 2 ). In 1987, all remaining wild condors were captured and bred, with juveniles released to the wild from 1992 onwards. Reintroduced birds are monitored regularly, and poisoned birds are treated with chelation therapy - where a drug binds to lead in the bloodstream and takes it to the kidneys to be filtered out. Since 1995, power line collisions have been avoided by giving juveniles behavioural training before reintroduction. Because of these measures, the California condor mortality rate in the wild decreased from 37.2% in 1992-1994 to 5.4% in 2001-2011. Challenges of conserving California condors Although captive breeding has saved the California condor population, it has also altered behaviours. The original condors stay with one mate longer than reintroduced condors, which may form polygamous relationships. Scientists think that spending so much time with non-family members in captivity has made juveniles promiscuous when reintroduced. Captive bred condors have also gotten used to being fed by people - so they approach people more often, spend longer in areas of human activity, and forage over a smaller area than the original condors. Moreover, condors in southern California were spotted feeding their chicks human litter. These behavioural changes mean the wild California condor population is not self-sustaining. The wild population is also not self-sustaining because condors are still being poisoned ( Figure 3 ). Banning lead bullets is the most effective way to guarantee population growth, but enforcing it has been challenging. Non-toxic alternative bullets like copper cannot find popularity. For population growth, every adult California condor killed is estimated to be worth 2-3 reintroduced juveniles. This is because released juveniles are more vulnerable and take years to reach breeding age. Therefore, American conservationists must keep pressuring authorities to reduce threats to adult California condors. Conclusion Pollution, urbanisation, and climate change have made it hard for the California condor population to recover from decades of lead poisoning. Long generation times and behavioural changes mean captive breeding is the species’ only hope of survival. Perhaps humans are the ones who need to change their behaviour - not feeding California condors and switching to copper bullets would allow these majestic birds to keep roaming the skies. Written by Simran Patel Related articles: Marine iguana conservation / Deception by African birds / Emperor penguins REFERENCES Bakker, V.J. et al. (2024) Practical models to guide the transition of California condors from a conservation-reliant to a self-sustaining species. Biological Conservation . 291: 110447. Available from: https://www.sciencedirect.com/science/article/pii/S0006320724000089 (Accessed 19th September 2024). D’Elia, J., Haig, S.M., Mullins, T.D. & Miller, M.P. (2016) Ancient DNA reveals substantial genetic diversity in the California Condor (Gymnogyps californianus) prior to a population bottleneck. The Condor . 118 (4): 703–714. Available from: https://doi.org/10.1650/CONDOR-16-35.1 (Accessed 28th September 2024). Finkelstein, M.E. et al. (2023) California condor poisoned by lead, not copper, when both are ingested: A case study. Wildlife Society Bulletin . 47 (3): e1485. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/wsb.1485 (Accessed 28th September 2024). Kelly, T.R. et al. (2015) Two decades of cumulative impacts to survivorship of endangered California condors in California. Biological Conservation . 191: 391–399. Available from: https://www.sciencedirect.com/science/article/pii/S0006320715300173 (Accessed 28th September 2024). Mee, A. & Snyder, N. (2007) California Condors in the 21st Century - conservation problems and solutions. In: 243–279. Meretsky, V.J., Snyder, N.F.R., Beissinger, S.R., Clendenen, D.A. & Wiley, J.W. (2000) Demography of the California Condor: Implications for Reestablishment. Conservation Biology . 14 (4): 957–967. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1523-1739.2000.99113.x (Accessed 29th September 2024). Stack, M.E. et al. (2022) Assessing Marine Endocrine-Disrupting Chemicals in the Critically Endangered California Condor: Implications for Reintroduction to Coastal Environments. Environmental Science & Technology . 56 (12): 7800–7809. Available from: https://doi.org/10.1021/acs.est.1c07302 (Accessed 19th September 2024). U.S. Fish and Wildlife Service (2023) California Condor Population Graph, 1980-2022 | FWS.gov . 18 April 2023. Available from: https://www.fws.gov/media/california-condor-population-graph-1980-2022 (Accessed 28th September 2024). U.S. Fish and Wildlife Service (2020) California Condor Recovery Program 2020 Annual Population Status . Available from: https://www.fws.gov/sites/default/files/documents/2020-California-Condor-Population-Status.pdf (Accessed 28th September 2024). Project Gallery

Is bacteria the key to unlocking this treatment? Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A breakthrough in endometriosis treatment 27/03/25, 12:05 Last updated: Published: 29/06/23, 09:16 Is bacteria the key to unlocking this treatment? In a giant leap forward, scientists have linked a specific bacterial infection to endometriosis for the very first time. Endometriosis is a condition in which the endometrium (lining of the uterus wall) grows outside of the uterus. For many women, the condition is characterised by debilitating pain, fatigue and infertility. The average time span for an accurate diagnosis is 7.5 years, with some women opting for a complete hysterectomy (removal of the uterus) to curb the pain. Unfortunately, the pathogenesis (the process by which a disease develops) of endometriosis is still relatively unknown. With previous scientific theories including retrograde menstruation, immune dysregulation, hormonal imbalance, stem cells and benign metastasis- this is the first time a bacterial theory has been forwarded. Dr Muraoka and his team theorised a link between bacterial localisation within the female reproductive tract and endometriosis- following promising research carried out on mice models. The Japanese study discovered a bacterium known as Fusobacterium to be present in the uteruses of 65% of women suffering from endometriosis, compared to less than 7% of women without the disease. Fusobacterium is a bacterium which is mostly found within the microbe of the mouth, gut and vagina. This bacterium has been linked to other inflammatory diseases such as gum disease. Follow-up studies- undertaken on mice- discovered that those treated with antibiotics saw a significant reduction in both size and frequency of lesions associated with the disease. Clinical trials are now forging ahead to investigate the effects of antimicrobials as a viable treatment option for endometriosis patients. This revolutionary study is the first of its kind and could see patient disease management progress away from medieval invasive procedures and decades of pain. For more information on Dr Muraoka and his team's work check out his study . Written by Kellie Leonard Related articles: Underreporting of endometriosis / Are PCOS and endometriosis sisters? / Gynaecology Project Gallery

Healthy heart, healthy mind Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link How does physical health affect mental health? Last updated: 16/10/25, 10:20 Published: 30/01/25, 08:00 Healthy heart, healthy mind Introduction Over the last decade, maintaining good mental health has become an increasing global priority. More people are committing time to self-care meditation, and other cognitive practices. We have also seen a rise in people taking care of their physical health through exercise and clean eating. This is fantastic – people are making time for one of the most important aspects of life, their health! But with the fast-paced nature of modern lifestyles, it is hard to devote separate time each week to purely mental and physical wellbeing. What if there were ways we could enhance both physical and mental wellbeing at the same time? Are both forms of health completely distinct from one another, or could a change in one have an effect on the other? If you’re looking for ways to improve your self-care efficiency, this may be the article for you! Healthy heart, healthy mind Physical health is a lot easier to define, on account of it being largely visible. Mental health on the other hand lacks much of a concrete definition. What is widely agreed is that emotions and feelings play a large part in making up our mental health. Emotions are largely determined by how we feel about our current internal and external environment, meaning bad bodily signs (as part of our internal environment) will have a negative effect on our overall mood. This is why being ill puts us in such a bad mood – even a blocked nose can annoy us by affecting how we do everyday activities. Poor fitness levels are likely no different – not being the most physically capable and finding everyday physical tasks challenging will likely have an effect on your mood and your confidence. Recent studies have backed up this idea, namely that signs of bodily inflammation are associated with increased risk of depression and negative mood. The role of neurotransmitters So being physically fit is associated with having better mental health, but does that mean exercise itself is mentally health as well, or is it just the effect of exercise that makes us happy? In other words, we seem to enjoy the result, but do we enjoy the process too? Studies have found that exercise increases dopamine levels in the brain. Dopamine is a neurotransmitter (a chemical messenger in the brain) that signals reward and motivation, similar to when we earn something for the work we put in ( Figure 1 ). Exercise is therefore seen as rewarding to the brain. There is also a lot of evidence suggesting exercise increases serotonin levels in both rats and humans. Serotonin is also a neurotransmitter, associated with directly enhancing mood and even having anti-depressant effects. Experiments in rats even suggest that increases in serotonin can decrease anxiety levels. Now, this does not mean exercise alone can cure anxiety disorder or depression, but could it be a useful variable in a clinical setting? Clinical uses Studies in depressive patients suggest that, yes, exercise does lead to better mental and physical health in patients with depression. This pairs well with another common finding that depressed patients are very rarely willing to complete difficult tasks for reward. So even on an extreme clinical scale, mental ill-health can have very damning consequences on maintaining good physical health. On the other hand, simple activities such as light jogs or walks may be the key to reversing negative spirals and getting on the right track towards recovery ( Figure 2 ). Conclusion and what we can do So far we have pretty solid evidence that mental health can impact physical health and vice versa, both negatively and positively. Going back to the introductory question, yes! We can find activities that improve both our physical and mental health. The trick is to find exercises that we find enjoyable and rewarding. On the clinical side, this could mean that physical exercise may be as effective at remitting depressive symptoms as antidepressants, likely with a lot fewer side effects. With that said, stay active and have fun, it helps more than you think! Written by Ramim Rahman Related articles: Environmental factors in exercise / Stress and neurodegeneration / Personal training / Mental health awareness REFERENCES Nord, C. (2024) The balanced brain . Cambridge: Penguin Random House. Osimo, E.F. et al. (2020) ‘Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls’, Brain, Behavior, and Immunity, 87, pp. 901–909. doi:10.1016/j.bbi.2020.02.010. Basso, J.C. and Suzuki, W.A. (2017) ‘The effects of acute exercise on mood, cognition, neurophysiology, and neurochemical pathways: A Review’, Brain Plasticity , 2(2), pp. 127–152. doi:10.3233/bpl-160040. [figure 1] DiCarlo, G.E. and Wallace, M.T. (2022) ‘Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates’, Neuroscience & Biobehavioral Reviews, 133, p. 104494. doi:10.1016/j.neubiorev.2021.12.017. [figure 2] Donvito, T. (2020) Cognitive behavioral therapy for arthritis: Does it work? what’s it like?, CreakyJoints. Available at: https://creakyjoints.org/living-with-arthritis/mental-health/cognitive-behavioral-therapy-for-arthritis/ (Accessed: 06 December 2024) Project Gallery

Setting Neuropsychiatry In a Wider Medical Context Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Schizophrenia, Inflammation and Accelerated Aging: a Complex Medical Phenotype 20/02/25, 11:54 Last updated: Published: 24/05/23, 09:45 Setting Neuropsychiatry In a Wider Medical Context In novel research by Campeau et al. (2022), the proteomic analysis of 742 proteins from the blood plasma of 54 schizophrenic participants and 51 age-matched healthy volunteers. This investigation resulted in the validation of the previously-contentious link between premature aging and schizophrenia by testing for a wide variation of proteins involved in cognitive decline, aging-related comorbidities, and biomarkers of earlier-than-average mortality. The results from this research demonstrated that age-linked changes in protein abundance occur earlier on in life in people with schizophrenia. This data also helps to explain the heightened incidence rate of age-related disorders and early all-cause death in schizophrenic people too, with protein imbalances associated with both phenomena being present in all schizophrenic age strata over age 20. This research is the result of years of medical intrigue regarding the biomedical underpinnings of schizophrenia. The comorbidities and earlier death associated with schizophrenia were focal points of research for many years, but only now have valid explanations been posed to answer the question of the presence of such phenomena. The explanation for the greater incidence rate of early death in schizophrenia was described in this study as the increased volume of certain proteins. Specifically, these included biomarkers of heart disease (Cystatin-3, Vitronectin), blood clotting abnormalities (Fibrinogen-B) and an inflammatory marker (L-Plastin). These proteins were tested for due to their inclusion in a dataset of protein biomarkers of early all-cause mortality in healthy and mentally-ill people published by Ho et al. (2018) for the Journal of the American Heart Association. Furthermore, a protein linked to degenerative cognitive deficit with age, Cystatin C, was present in increased volume in schizophrenic participants both under and over the age of 40. This explains why antipsychotics have limited effectiveness in reducing the cognitive effects of schizophrenia. In this study, schizophrenics under 40 had similar plasma protein content as the healthy over-60 strata set, including both biomarkers of cognitive decline, age-related diseases and death. Schizophrenics under-40 showed the same likelihood for incidence of the latter phenomena compared to the healthy over-60 set. These results could demonstrate the necessity for use of medications often used to treat age-related cognitive decline and mortality-linked protein abundances to treat schizophrenia. One of these options include polyethylene glycol-Cp40, a C3 inhibitor used to treat nocturnal haemoglobinuria, which could be used to ameliorate the risk of developing age-related comorbidities in schizophrenic patients. This treatment may be effective in the reduction of C3 activation, which would reduce the opsonisation (tagging of detected foreign products in blood). When overexpressed, C3 can cause the opsonisation of healthy blood cells in a process called haemolysis, which can catalyse the reduction of blood volume implicated in cardiac events and other comorbidities. However, whether or not this treatment would benefit those with schizophrenia is yet to be proven. The potential of this research to catalyse new treatment options for schizophrenia cannot be understated. Since the publication of Kilbourne et al. in 2009, the impact of cardiac comorbidities in catalysing early death in schizophrenic patients has been accepted medical dogma. The discovery of exact protein targets to reduce the incidence rate of age-linked conditions and early death in schizophrenia will allow the condition to be treated more holistically, with greater observance to the fact that schizophrenia is not only a psychiatric illness, but also a neurocognitive disorder with affiliated comorbidities that have to be prevented adequately. Written by Aimee Wilson Related articles: Genetics of ageing and longevity / Ageing and immunity / Inflammation therapy Project Gallery !

Why chirality is important in developing drugs Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Chirality in drugs 04/02/25, 15:50 Last updated: Published: 06/06/23, 16:53 Why chirality is important in developing drugs Nearly 90% of the drugs currently on the market are racemates, which are composed of an equimolar mixture of two enantiomers, and approximately half of all drugs are chiral compounds. Chirality is the quality of an item that prevents it from superimposing on its mirror counterpart, similar to left and right hands. Chirality, a generic characteristic of "handedness,"plays a significant role in the creation of several pharmaceutical drugs. It's interesting to note that 20 of the 35 drugs the Food and Drug Administration (FDA) authorised in 2020 are chiral drugs. For example, Ibuprofen, a chiral 2-aryl propionic acid derivative, is a common over-the-counter analgesic, antipyretic, and anti-inflammatory medication. However, Ibuprofen and other medications from similar families can have side effects and risks related to their usage. Drugs of the chiral class have the drawback that only one of the two enantiomers may be active, while the other may be ineffective or have some negative effects. The inactive enantiomer can occasionally interact with the active enantiomer, lowering its potency or producing undesirable side effects. Additionally, Ibuprofen and other members of the chiral family of pharmaceuticals can interact with other drugs, including over-the-counter and prescription ones. To guarantee that only the active enantiomer is present in chiral-class medications, it is crucial for pharmaceutical companies to closely monitor their production and distribution processes. Lessening the toxicity or adverse effects linked to the inactive enantiomer, medical chemistry has recently seen an increase in the use of enantiomerically pure drugs. In any instance, the choice of whether to utilise a single enantiomer or a combination of enantiomers of a certain medicine should be based on clinical trial results and clinical competence. In addition to requests to determine and control the enantiomeric purity of the enantiomers from a racemic mixture, the use of single enantiomer drugs may result in simpler and more selective pharmacological profiles, improved therapeutic indices, simpler pharmacokinetics, and fewer drug interactions. Although, there have been instances where the wrong enantiomer results in unintended side effects, many medications are still used today as racemates with their associated side effects; this issue is probably brought on by both the difficulty of the chiral separation technique and the high cost of production. In conclusion, Ibuprofen and other medications in the chiral family, including those used to treat pain and inflammation, can be useful, but they also include a number of dangers and adverse effects. It's critical to follow a doctor's instructions when using these medications and to be aware of any possible interactions, allergic reactions, and other hazards. To maintain the security and efficacy of medicines in the chiral class, pharma producers also have a duty to closely monitor their creation and distribution. Written by Navnidhi Sharma Project Gallery

A Scientia News Biology and Genetics collaboration Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Germline gene therapy (GGT): its potential and problems 09/07/25, 14:14 Last updated: Published: 21/01/24, 11:47 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. 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