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Neuromyelitis optica is also known as Devic disease Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Neuromyelitis optica – how is it different to multiple sclerosis? 10/07/25, 10:25 Last updated: Published: 13/07/24, 10:56 Neuromyelitis optica is also known as Devic disease This is article no. 6 in a series on Rare Diseases. Next article: Apocrine carcinoma . Previous article: Unfolding prion diseases . If you have never heard of neuromyelitis optica (NMO), you’re not alone! NMO is a rare disease affecting the spinal cord and optic nerve. A disease is determined as rare when it affects less than 1 in 2000 people. NMO, Devic’s disease in layman’s term, is an autoimmune disease, which means the immune system fails and attacks healthy self-cells, and can be one-off or recurrent. When patients experience a NMO attack, symptoms like eye pain and weakness in limbs, caused by inflammation of the spinal cord (transverse myelitis) and optic nerve (optic myelitis), commonly occur. There is a much higher prevalence of females with NMO than males. The exact reasons are still being researched, but some suggest it could be due to hormonal, genetic, and epigenetic factors, including the gut microbiome. Currently, there is no cure to this sudden and perplexing disease, yet medication to suppress the immune system and reduce inflammation are prescribed to patients. So the question arises – what causes NMO? In short, we don’t know yet. However, we do understand that 90% of NMO cases are caused by NMO-specific antibodies against Aquaporin4 (AQP4), an intrinsic membranes protein highly concentrated in the spinal cord and the brain, specifically in astrocytes and ependymal cells lining in the ventricles. AQP4 are water-selective channels in many plasma membranes and are responsible for maintaining brain-water homeostasis. Did you know NMO is often mistaken as Multiple Sclerosis (MS)? MS is also an autoimmune system and has similar symptoms as NMO, such as vision and mobility difficulties. However, there are important differences between the two. NMO specifically targets the optic nerves and spinal cord, leading to more severe attacks that can cause blindness and paralysis if not treated promptly. On the other hand, MS affects the brain and spinal cord more diffusely. Diagnosis and treatment for NMO and MS can be quite different, making it crucial to correctly distinguish between the two conditions. Advanced techniques like MRI scans, blood tests for specific antibodies (like AQP4-IgG for NMO), and careful clinical evaluation help doctors make the right diagnosis and provide appropriate treatment. Understanding these distinctions is vital for effective management and improving the quality of life for those affected by these diseases. Written by Chloe Kam Related article: Neuroimaging REFERENCES Hor, J.Y., Asgari, N., Nakashima, I., Broadley, S.A., Leite, M.I., Kissani, N., Jacob, A., Marignier, R., Weinshenker, B.G., Paul, F., Pittock, S.J., Palace, J., Wingerchuk, D.M., Behne, J.M., Yeaman, M.R. and Fujihara, K. (2020). Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide. Frontiers in Neurology , 11. doi: https://doi.org/10.3389/fneur.2020.00501 . Kim, S.-M., Kim, S.-J., Lee, H.J., Kuroda, H., Palace, J. and Fujihara, K. (2017). Differential diagnosis of neuromyelitis optica spectrum disorders. Therapeutic Advances in Neurological Disorders , 10(7), pp.265–289. doi: https://doi.org/10.1177/1756285617709723 . Mader, S. and Brimberg, L. (2019). Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease. Cells , 8(2), p.90. doi: https://doi.org/10.3390/cells8020090 . Project Gallery

Life's origins Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The genesis of life 11/07/25, 10:04 Last updated: Published: 23/11/23, 11:22 Life's origins Did the egg or the chicken come first? This question is often pondered regarding life’s origin and how biological systems came into play. How did chemistry move to biology to support life? And how have we evolved into such complex organisms? The ingredients, conditions and thermodynamically favoured reactions hold the answer, but understanding the inner workings of life’s beginnings poses a challenge for us scientists. Under an empirical approach, how can we address these questions if these events occurred 3.7 billion years ago? The early atmosphere of the Earth To approach these questions, it is relevant to understand the atmospheric contents of the primordial Earth. With a lack of oxygen, the predominant make-up included C02, NH3 and H2, creating a reducing environment for the drive of chemical reactions. When the earth cooled, and the atmosphere underwent condensation, pools of chemicals were made - this is known as “primordial soup”. It is thought that reactants could collide from this “soup” to synthesise nucleotides by forming nitrogenous bases and bonds, such as glycosidic or hydrogen bonds. Such nucleotide monomers were perhaps polymerised to create long chains for nucleic acid synthesis, that is, RNA, via this abiotic synthesis. Thus, if we have nucleic acids, genetic information could have been stored and passed later down the line, allowing for our eventual evolution. Conditions for nucleic acid synthesis The environment supported the formation of monomers for said polymerisation. For example, hydrothermal vents could have provided the reducing power via protons, allowing for the protonation of structures and providing the free energy for bond formation. Biology, of course, relies on protons for the proton gradient in ATP synthesis at the mitochondrial membrane and, in general, acid-base catalysis in enzymatic reactions. Therefore, it is safe to say protons played a vital role in life’s emergence. The eventual formation of structures by protonation and deprotonation provides the enzymatic theory of life’s origins. That is, some self-catalytic ability for replication in a closed system and the evolution of complex biological units. This is the “RNA World” theory, which will be discussed later. Another theory is wet and dry cycling at the edge of hydrothermal pools. This theory Is provided by David Deamer, who suggests that nucleic acid monomers placed in acidic (pH 3) and hot (70-90 degrees Celsius) pools could undergo condensation reactions for ester bond formation. It highlights the need for low water activity and a “kinetic trap” in which the condensation reaction rate exceeds the hydrolysation rate. The heat of the pool provides a high activation energy for the localised generation of polymers without the need for a membrane-like compartment. But even if this was possible and nucleic acids could be synthesised, how could we “keep them safe”? This issue is addressed by the theory of "protocells" formed from fatty acid vesicles. Jack Szostak suggests phase transition (that is pH decrease) allowed for the construction of bilayer membranes from fatty acid monomers, which is homologous to what we see now in modern cells. The fatty acids in these vesicles have the ability to “flip-flop” to allow for the exchange of nutrients or nucleotides in and out of the vesicles. It is suggested that clay encapsulated nucleotide monomers were brought into the protocell by this flip-flop action. Vesicles could grow by competing with surrounding smaller vesicles. Larger vesicles are thought to be those harbouring long polyanionic molecules - that is RNA - which creates immense osmotic pressure pushing outward on the protocell for absorption of smaller vesicles. This represents the Darwinian “survival of the fittest” theory in which cells with more RNA are favoured for survival. The RNA World Hypothesis DNA is often seen as the “Saint” of all things biology, given its ability to store and pass genetic information to mRNA and then mRNA can use this information to synthesise polypeptides. This is the central dogma of course. However, the RNA world hypothesis suggests that RNA arose first due to its ability to form catalytic 3D structures and store genetic information that could have allowed for further synthesis of DNA. This makes sense when you think about how the primer for DNA replication is formed out of RNA. If RNA did not come first, how could DNA replication be possible? Many other scenarios suggest RNA evolution preceded that of DNA. So, if RNA arose as a simple polymer, its ability to form 3D structures could have allowed ribozymes (RNA with enzymatic function) within these protocells. Ribozymes, such as RNA ligase and polymerase, could have allowed for self-replication, and then mutation in primary structure could have allowed evolution to occur. If we have a catalyst, in a closed system, with nutrient exchange, then why would life’s formation not be possible? But how can we show that RNA can arise in this way? The answer to this is SELEX - selective evolution of ligands by exponential enrichment (5). This system was developed by Jack Szostak, who wanted to show the evolution of complex RNA, ribozymes in a test tube was possible. A pool of random, fragmented RNA molecules can be added to a chamber and run through a column with beads. These beads harbour some sequence or attraction to the RNA molecules the column is selecting for. Those that attach can be eluted, and those that do not can be disregarded. The bound RNA can be rerun through SELEX, and the conditions in the column can be more specific in that only the most complementary RNAs bind. This allowed for the development of RNA ligase and RNA polymerase - thus, self-replication of RNA is possible. SELEX helps us understand how the evolution of RNA in the primordial Earth could have been possible. This is also established by meteorites, such as carbon chondrites that burnt up in the earth’s atmosphere encapsulating the organic material in the centre. Chondrites found in Antarctica have been found to contain 80+ amino acids (some of which are not compatible with life). These chondrites also included nucleobases. So, if such monomers can be synthesised in a hostile environment in outer space/in our atmosphere, then the theory of abiotic synthesis is supported. Furthermore, it is relevant to address the abiotic synthesis of amino acids since the evolution of catalytic RNA could have some complementarity for polypeptide synthesis. Miller and Urey (1953) set up a simple experiment containing gas representing the early primordial earth (Methane, hydrogen, ammonia, water). They used a conduction rod to provide the electrical discharge (meant to simulate lightning or volcanic eruption) to the gases and then condensed them. The water in the other chamber turned pink/ brown. Following chromatography, they identified amino acids in the mixture. These simple manipulations could have been homologous to early life. Conclusion The abiotic synthesis of nucleotides and amino acids for their later polymerisation would support the theories that address chemistry moving toward biological life. Protocells containing such polymers could have been selected based on their “fitness” and these could have mutated to allow for the evolution of catalytic RNA. The experiments mentioned represent a small fragment of those carried out to answer the questions of life’s origins. The evidence provides a firm ground for the emergence of life to the complexity of what we know today. Written by Holly Kitley Project Gallery

The human race has witnessed ten influenza pandemics over the course of 300 years. COVID-19, the most recent, killed approximately 6.9 million people and infected nearly 757 million. Go Back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The world vs the next pandemic Last updated: 18/11/24 Published: 25/03/23 The human race has witnessed ten influenza pandemics over the course of 300 years. COVID-19, the most recent, killed approximately 6.9 million people and infected nearly 757 million. Though seemingly quite large, the number of deaths caused by the coronavirus is still comparatively fewer than the pandemics of the past, which have killed around 50–100 million people globally. These large numbers may seem like statistics from a century ago, but many scientists predict the same-scale destruction with future pandemics, heightening the concern about how prepared we are when the next big outbreak strikes. It is impossible to know when the next pandemic will hit or the number of casualties it will bring. The only certainty is that it cannot be avoided, which raises the question of how to mitigate the impact and reduce the effectiveness of large-scale losses. During the COVID-19 outbreak, we observed that preventive measures such as social distancing and face coverings could intervene in viral transmission to some degree. Additionally, strategies like complete lockdown, isolation and timely treatment can help in the containment and recovery of those already infected. These measures, however, can only be taken once the threat is detected promptly before infecting a larger population. To prevent an infection from becoming an outbreak, strategies that focus on the source of the disease can prove to be highly advantageous. Preventive measures may include: ● monitoring the mobilisation of wildlife that potentially carries harmful pathogens ● studying the interactions between different species in wildlife ● surveillance of the domestic and international markets for wildlife trade and strict imposition of biosecurity laws. Additionally, an effort needs to be made for sharing the generated data with global laboratories to promote scientific collaboration. Once the threat is identified, quick decision-making using the correct precautions needs to take place. Simultaneously, investments in research sectors promoting mRNA vaccine developments, novel drug treatments, and emerging technological advances need to be increased. In conclusion, the strategies for the management of the next pandemic need to operate on a multi-level governance with optimal coordination between different institutions involved in crisis management. There is a constant threat of pandemics looming over the world. The outbreak is inevitable, but its effect solely depends on the preparedness and response of the governmental bodies and global health institutions. Is it going to be a hurricane of destruction, or will it just pass by like a gush of wind? Only time will tell. Written by Navnidhi Sharma Related articles: Diabetes mellitus as an epidemic / Are pandemics becoming less severe? REFERENCES Coccia, M. (2021). Pandemic Prevention: Lessons from COVID-19. Encyclopedia, 1(2), 433–444. https://doi.org/10.3390/encyclopedia1020036 Cockerham, W. C., & Cockerham, G. B. (2021). The COVID-19 reader: the science and what it says about the social. Routledge. Frieden, T. R., Buissonnière, M., & McClelland, A. (2021). The world must prepare now for the next pandemic. BMJ Global Health, 6(3), e005184. https://doi.org/10.1136/bmjgh-2021-005184 Garrett, L. (2005). The Next Pandemic. Foreign Af airs, 84, 3. https://heinonline.org/HOL/LandingPage?handle=hein.journals/fora84&div=61&id=&page= WORLD HEALTH ORGANISATION. (2022). WHO Coronavirus (COVID-19) Dashboard. Covid19.Who. int. https://covid19.who.int/?mapFilter=deaths World Economic Forum. (2021, November 30). COVID-19: How much will it cost to prepare the world for the next pandemic? World Economic Forum. https://www.weforum.org/agenda/2021/11/preparing-for-next-pandemic-covid-19

Lesser-known illnesses Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Rare zoonotic diseases 10/07/25, 10:33 Last updated: Published: 08/07/23, 13:34 Lesser-known illnesses This is article no. 1 in a series on rare diseases. Next article: Breast cancer in males . Introduction From COVID-19 possibly coming from livestock in Wuhan market to HIV resulting from numerous transmissions between African primates, it seems that zoonotic diseases are difficult to control. They occur when pathogenic microorganisms are spread from animals to humans or vice-versa. Their impact on human civilization is alarming because they are responsible for 2.5 billion cases of illness and 2.7 million deaths in humans annually around the world. Although there is a lot of information regarding more familiar zoonotic diseases such as rabies and malaria, this article focuses on those that may be less discussed as they could become more problematic in the future. Crimean-Congo haemorrhagic fever (virus) To begin, Crimean-Congo haemorrhagic fever (CCHF) is a viral disease, which spreads when humans are bitten by ticks carrying the virus along with farmers killing infected livestock. It is endemic in more than 30 European, African and Asian countries with the exact factors contributing to the increased cases of CCHF being a mystery. Diagnosing the disease involves detecting the virus through Enzyme-linked immunosorbent assay (ELISA), real time polymerase chain reaction (RT-PCR) along with detecting IgM and IgG antibodies using ELISA. As for the treatment options for CCHF, they are finite as there are no available vaccines and the only antiviral drug used against the virus is ribavirin, which prevents replication of various DNA and RNA viruses in-vitro. Given all this information, it is evident that extensive research is necessary to better understand the disease holistically and design drugs that can stop more fatalities associated with CCHF. Trichinellosis (parasite) The next zoonotic disease to address is trichinellosis or trichinosis , which is caused by Trichinella spiralis and so it is a parasitic infection. It can spread by eating poorly prepared meat such as pork and mammals like horses and wild carnivores are typically the reservoirs of infection. Its epidemiology in humans seems to be limited because it has 10,000 cases and 0.2% death rate annually. Moreover, an important factor that can contribute to the spread of trichinellosis is culture because certain communities have dishes containing raw meat. For example, a review referenced more than 600 outbreaks, 38,797 infections and 336 deaths in humans between 1964 and 2011 in China. As for diagnosing trichinellosis, it is challenging because it has general signs. With this in mind, the common method to spot the disease is detecting IgG antigens that work against Trichinella spiralis . On the other hand, its major drawback is getting a false negative in early trichinellosis infection. Like CCHF, trichinellosis is not as prevalent compared to other zoonotic diseases but it can have devastating impacts on specific countries, so increasing the supply of antiparasitic drugs like albendazole and/or mebendazole would be beneficial to stop the spread of Trichinella spiralis. Brucellosis (bacteria) The next zoonotic disease which is caused by a bacterial pathogen is brucellosis and is common worldwide, though certain places have higher prevalence of the disease compared to others. The pathogen can be transmitted through various ways such as direct contact with infected animal tissue on broken skin and consuming contaminated meat or dairy. Interestingly, it has been linked to childhood pulmonary infections as 18 out of 98 brucellosis patients have experienced such symptoms, but this is rare. The graph above indicates that when brucellosis occurs in animals, it has a high likelihood of being passed onto humans. For example, the years 2004-2007 could be when brucellosis cases were most frequent. This could have been alleviated through specific antibiotics used to treat brucellosis that include rifampin, doxycycline and streptomycin. Similar to trichinellosis, brucellosis diagnosis can be difficult because the symptoms can vary and are not exclusive to one disease, suggesting that different laboratory techniques are needed to find brucellosis in patients. Conclusion It looks like there is a recurring pattern of the zoonotic diseases outlined in this article occurring in developing countries as opposed to developed countries. As such, there have to be more effective interventions to prevent their ramifications on populations living in these countries. For this to occur, there has to be sufficient information, awareness, and education of these rarer zoonotic diseases to begin with. Furthermore, the current treatments for CCHF, trichinellosis and brucellosis may be unsuccessful due to the threat of antimicrobial resistance, hence finding alternative treatments for the aforementioned zoonotic diseases is vital in the future. Written by Sam Jarada Related articles: Rabies / Canines and cancer / Vaccine for malaria Project Gallery

Also known as Major Depressive Disorder (MDD) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link What does depression do to your brain? 14/07/25, 15:12 Last updated: Published: 10/10/24, 11:19 Also known as Major Depressive Disorder (MDD) This is Article 1 in a series on psychiatric disorders and the brain. Next article: Inside out: the chemistry of depression. -- I affect 3.8% of the population wide, With 280 million voices struggling inside. In women, my reach is 6%, And 5.7% of those over 60 feel me. Among new mothers, I reach 10%, With over 700,000 lost to my torment each year. What am I? Depression. The most prevalent psychiatric disorder that costs both money and lives. -- Also known as Major Depressive Disorder (MDD), depression is a heterogenous disease, which means the manifestation of the disorder is influenced by multiple genes. It is commonly known that consistent low mood, loss of interest in hobbies you used to enjoy, lethargy, feeling of hopelessness etc. are physical symptoms of depression. However, have you ever wondered what happens in the brain in a depression sufferer, from the neuroscience aspect? Structurally, research into the neuroscience of depression reveals significant structural abnormalities in the brains of affected individuals. Studies using structural magnetic resonance imaging (MRI) have shown that those with MDD show reductions in gray matter volume in regions responsible for emotion regulation. The limbic system of the brain is responsible for producing and regulating emotions. In depressed individuals, the hippocampus—a key component of the limbic system—shows reduced gray matter volume, which is linked to abnormalities in the associated white matter tracts. White matter consists of myelinated axons that facilitate communication between different brain regions, while grey matter contains the neuronal cell bodies responsible for processing information. The presence of abnormalities in white matter suggests a disconnection between regions within the limbic system, potentially impairing their ability to communicate effectively. This disconnection may contribute to the emotional dysregulation observed in depression, highlighting the intricate relationship between grey and white matter in the pathology of this disorder. Depression is a complex disorder that not only affects mood but changes the structure and function of the brain. By understanding the neurobiological changes—including reductions in grey matter and white matter disconnections—we can better grasp the pathogenesis of this condition. Continued research in the neuroscience behind depression is essential for developing more effective treatments. There is still much more to explore and understand in depression research; with each new discovery, we realise how much more there is to learn. Written by Chloe Kam Related article: Depression in children Project Gallery

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

The unique condition of microgravity Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Astronauts in space… losing gravity, losing immunity? 09/07/25, 10:58 Last updated: Published: 08/09/24, 13:39 The unique condition of microgravity Introduction Since the first successful human launch to space on April 12th, 1961, over 600 astronauts have travelled beyond the Earth’s atmosphere. Space travel is essential in driving technological innovation and consistently increases our understanding of the cosmos. However, alongside the thrill of space exploration, astronauts face significant challenges, including profound risks to their immune systems. Astronauts in space endure a unique condition of near weightlessness known as microgravity, which often causes dysregulation of their immune systems. Effect of microgravity on T-cell immunity One of the critical studies emphasising the effects of microgravity on the immune system is a twin study conducted by NASA, where they compared various gene expression datasets between an astronaut who had been on the International Space Station (ISS) for one year and their identical twin who had not travelled to space. They discovered changes in the methylation patterns of immunologically relevant genes such as NOTCH3 and SLC1A5 , which are both crucial in T cell development. They also found microgravity caused an increase in pro-inflammatory molecules and decreased anti-inflammatory molecules, alluding to spaceflight causing an increased inflammatory state. These patterns are consistent with other experiments simulating microgravity conditions, such as prolonged bed rest models. Microgravity has also been shown to induce thymic atrophy, which is when the thymus slowly shrinks and loses its function. The thymus is a primary lymphoid organ that is crucial in T cell development. An experiment performed on the International Space Station (ISS) has shown that exposing mice to 1g gravity can alleviate microgravity-induced thymic atrophy ( Figure 1 ), suggesting that exposure to a standard gravitational field is a potential treatment. The thymic environment is altered due to microgravity. In particular, thymic epithelial cells (TECs) are misplaced and, therefore cannot perform their role in T cell maturation. Overall, there is a significant decrease in the output of T cells from the thymus, shown by a clear decrease in thymic mass and alterations in gene expression related directly to the process of T cell differentiation. Effect of microgravity on the bone marrow Furthermore, microgravity affects the bone marrow, another primary lymphoid organ. The bone marrow consists of many mesenchymal stem cells (MSCs), which differentiate hematopoietic stem cells (HSCs) into leukocytes. Microgravity inhibits osteogenesis and promotes adipogenesis, which means that bone formation is slowed down, but fat cell production is increased. This happens due to the changes to the structure inside the cell, known as actin cytoskeleton, which affects transcriptional regulators, which generally control cell differentiation. In space, there is also suppression of the cytokine CXCL2 in MSCs, which affects HSC differentiation into immune cells, indicating a link between MSC dysfunction and immunosuppression faced by astronauts. Other factors affecting the immune system Microgravity is the main factor behind immune system dysregulation in astronauts, but other factors, such as stress and exposure to cosmic radiation, also play a role. Cosmic radiation can damage DNA, leading to mutations that impair the immune system’s ability to function properly. Stress hormones are known to affect immune system function. For instance, cortisol can reduce the number of leukocytes in circulation. Conclusion Due to the compromised state of the astronauts’ immune systems, latent viruses often reactivate. Herpes viruses, such as varicella-zoster virus (chickenpox!) and Epstein-Barr virus, have been documented to be reactivated in astronauts during and after space flight. This is mainly due to the loss of T cell immunity ( Figure 2 ) and a reduction in NK cell potency and number. Microgravity affects NK cells by changing their cytoskeletal form, which they need to perform cytotoxic functions. Understanding and mitigating the risks of space travel is crucial as more prolonged and ambitious missions are planned, such as sending humans to Mars. The primary medical countermeasure for the reactivation of herpes viruses is re-vaccination. However, at this current point, only a vaccine for varicella-zoster virus is available. Future research focusing on artificial gravity and environmental changes on spacecraft and the ISS may provide a safer journey for astronauts spending extended time in space. Written by Devanshi Shah Related articles: AI in space / The role of chemistry in space REFERENCES Akiyama, T., Horie, K., Hinoi, E., Hiraiwa, M., Kato, A., Maekawa, Y., Takahashi, A. & Furukawa, S. (2020) How does spaceflight affect the acquired immune system? npj Microgravity. 6 (1), 1–7. doi:10.1038/s41526-020-0104-1. Simon N. Archer, Carla Möller-Levet, María-Ángeles Bonmatí-Carrión, Emma E. Laing, Derk-Jan Dijk. Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest -ScienceDirect. https://www-sciencedirect.com.iclibezp1.cc.ic.ac.uk/science/article/pii/S2589004224005522?via%3Dihub [Accessed: 16 August 2024]. Hicks J, Olson M, Mitchell C, Juran CM, Paul AM. The Impact of Microgravity on Immunological States. Immunohorizons. 2023 Oct 1;7(10):670-682. doi: 10.4049/immunohorizons.2200063. PMID: 37855736; PMCID: PMC10615652. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight | Science. https://www.science.org/doi/10.1126/science.aau8650 [Accessed: 16 August 2024]. Hicks, J., Olson, M., Mitchell, C., Juran, C.M. & Paul, A.M. (2023) The Impact of Microgravity on Immunological States. ImmunoHorizons. 7 (10), 670–682. doi:10.4049/immunohorizons.2200063. Hobbs, Z. (2023) How many people have gone to space? | Astronomy.com. Astronomy Magazine. https://www.astronomy.com/space-exploration/how-many-people-have-gone-to-space/ . Mehta, S.K., Laudenslager, M.L., Stowe, R.P., Crucian, B.E., Feiveson, A.H., Sams, C.F. & Pierson, D.L. (2017) Latent virus reactivation in astronauts on the international space station. npj Microgravity. 3 (1), 1–8. doi:10.1038/s41526-017-0015-y. Surrey, U. Microgravity found to cause marked changes in gene expression rhythms in humans. https://phys.org/news/2024-03-microgravity-gene-rhythms-humans.html [Accessed: 16 August 2024]. Project Gallery

Hydrogen fuel cells generate electricity through an electrochemical reaction between hydrogen and oxygen Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Are hydrogen cars the future of the UK? 09/07/25, 10:53 Last updated: Published: 01/01/25, 13:50 Hydrogen fuel cells generate electricity through an electrochemical reaction between hydrogen and oxygen Introduction With the London debut of the first ever hydrogen powered racing car in June 2024, the new off-road racing series, Extreme H, is set to make waves in the motorsport and sustainability industries with its first season in 2025. The first ever hydrogen powered motorsport series was announced in 2022 to replace the carbon-neutral electric racing series Extreme E, with the intention of pioneering the potential of hydrogen fuel cells and diversifying the paths of sustainable mobility. Like its predecessor, Extreme H will continue to race off-road in a spec SUV car, where engineers and machinists from competing teams optimise the SUV for the different range of terrains and topographies. The hydrogen spec SUV, fittingly called the Pioneer 25 ( Figure 1 ), is promising for the rapid advancement of hydrogen fuel research, leading to the integration of hydrogen fuel cells vehicles on local roads. In line with the upcoming ban on the sale of new petrol, diesel, and hybrid cars across the UK in 2035, as well as the UK target of reaching carbon neutral by 2050, the need for sustainable and practical transport options is growing. So far however, electric cars have proved to not be a one-size-fits-all solution. Hydrogen fuel could potentially be the key to filling this gap. EVs vs. HFCVs Working mechanisms Hydrogen Fuel Cell Vehicles (HFCVs): Hydrogen fuel cells generate electricity through an electrochemical reaction between hydrogen and oxygen. The electricity produced is used to power an electric motor, which drives the car. The only byproduct of this process is water vapour. Electric Vehicles (EVs): A motor is powered directly from a charged battery, and equally produces no harmful emissions. As a result of large investments, electric vehicles have already established a strong footing in the UK market, prompting the declining cost of batteries as well as increasing availability of EV charging points in the UK. However, for many households and commercial uses, electric vehicles are not accessible forms of transport due to key barriers including the extensive charging time (around 8 hours), the weight of batteries for large vehicles, and performance decline in cold weather due to lithium-ion batteries being highly sensitive to temperature. HFCVs directly address these problems and present a sustainable and competitive alternative. As the refuelling process is the same as petrol and diesel cars, fuel tanks can be filled in the space of a few minutes and are notably weight efficient. A heavy-duty electric vehicle on the other hand can require a battery of around 7000 kg. Advantages of HFCVs: Significantly shorter refuelling times Can achieve 300-400 miles on a full tank Maintain performance in cold weather and under heavy loads Lighter and more energy-dense than electric vehicles Disadvantages: Expensive as they’re not yet widely available Lack of refuelling infrastructure The current primary method of hydrogen production produces CO2 as a byproduct Despite the key advantages hydrogen cars offer, there are currently only 2 available models of HFC cars in the UK, including the Toyota Mirai ( Figure 2 ) and the Hyundai Nexo SUV. As a result, there are currently fewer than 20 refuelling stations available nationwide, compared to the many thousands of charging points available across the country for electric vehicles. One of the main reasons why progress in hydrogen fuel production has been so delayed is because hydrogen, despite being the most abundant element in the universe, is only available on earth in compound form and needs to be extracted using chemical processes. The true sustainability of hydrogen production There are currently two main methods to extract hydrogen from nature, including steam-methane reforming and electrolysis. Hydrogen is colour-graded by production method to indicate whether it is renewable. Green/ yellow hydrogen The cleanest process for hydrogen production is electrolysis, where a current separates hydrogen from pure water. If the current is sourced from renewable energy, it’s known as green hydrogen. If it’s connected via the grid, then it’s called yellow hydrogen. The source of electricity is particularly important because the electrolysis process is about 75% efficient, which translates to higher costs yet cleaner air. Grey/ blue hydrogen Hydrogen can also be produced by treating natural gas or methane with hot steam. During this process, the methane splits into its four hydrogen atoms while one carbon atom bonds to oxygen and enters the atmosphere as carbon dioxide. This is known as grey hydrogen. If the carbon dioxide can be captured and stored via direct air capture, it’s called blue hydrogen. About 95% of all hydrogen in Europe is produced by methane steam reforming (grey and blue hydrogen), as it is very energy efficient and uses up lots of natural gas in the process, a resource that is quickly diminishing in importance and value as more and more households switch from gas boilers to heat pumps. Two percent of the world’s carbon emissions comes from the grey hydrogen process to produce ammonia for fertiliser and for steel production. For context, this is almost the same as the entire aviation industry. For HFCVs to be a truly sustainable alternative to combustion engines, green hydrogen via electrolysis (or another clean process) needs to be more widely available and economically viable. The UK’s plans for hydrogen As part of the UK hydrogen strategy ( Figure 3 ), the UK aims to reach up to 10GW or low carbon hydrogen production by 2030 (or equivalent to the amount of gas consumed by 3 million households in the UK annually). The government has allocated £240 million to develop hydrogen production and infrastructure. This is particularly for industry uses in the production of steel and cement, and for heavy goods vehicles (HGVs). Plans were also made to extend the use of hydrogen to heat homes, starting with ‘hydrogen village trials’ in 2025, to inform how 100% hydrogen communities would work, although this has understandably been met with local opposition. With greater research, information, and development into hydrogen for domestic uses, the applications of hydrogen energy may extend from industry and transport to households. As car companies (particularly Toyota, Hyundai, and BMW) continue to develop hydrogen car makes, and further investment is made into increased refuelling infrastructure and hydrogen fuel cell research, as well as with the ban on the sale of new combustion engine cars by 2035, commercial hydrogen cars have the potential to be commonly found on UK roads by 2040. Conclusion For now, HFCVs remain in the early stages of development, however they present a promising opportunity for the UK to diversify its clean transport options, particularly in areas where EV technology faces limitations such as for heavy goods vehicles. Rather than being competitors, it is likely that EVs and HFCVs will soon coexist, with each technology serving different needs. The biggest barrier to the progress of HFCVs currently is developing a full hydrogen refuelling infrastructure, where the gas is produced and then transported to stations across the nation, will take billions of pounds and a number of years to develop. If these initial hurdles could be overcome, HFCV technology can quickly become more practically and financially accessible. Written by Varuna Ganeshamoorthy Related articles: Electric vehicles / Nuclear fusion Project Gallery

Treatment that effectively controls tumours and prolongs survival without side effects Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A breakthrough in prostate cancer treatment 08/07/25, 14:35 Last updated: Published: 04/04/24, 16:00 Treatment that effectively controls tumours and prolongs survival without side effects Introduction Prostate cancer is a devastating disease that affects millions of men worldwide. Despite advancements in treatment options, aggressive forms of the disease, such as metastatic castrate-resistant prostate cancer (mCRPC), remain a major challenge. However, a recent study conducted by researchers at the University of Chicago Medicine Comprehensive Cancer Centre has established a promising "proof-of-concept" for a new treatment approach that could revolutionize the field. The study, published in Clinical Cancer Research, demonstrated the remarkable effectiveness of this novel treatment in a mouse model of advanced prostate cancer. The researchers achieved complete tumour control and long-lasting survival without any side effects. These ground-breaking findings have paved the way for further investigation in human clinical trials. Finding the exact cancer cell and then destroying it but leaving the healthy tissue untouched. In theory, it could be like aiming and shooting at someone in the video game but real world is a bit different, isn’t it? Overcoming Resistance to Hormonal Therapy Hormonal therapy, specifically androgen deprivation therapy (ADT), is the standard treatment for metastatic prostate cancer. However, the majority of patients eventually develop resistance to this therapy, leading to castrate-resistant prostate cancer. This resistance poses a significant challenge for clinicians and leaves patients with limited treatment options. Dr. Akash Patnaik, an accomplished physician-scientist and renowned expert in prostate cancer research and treatment, and his team at the University of Chicago Medical Centre have been exploring new strategies to overcome this resistance. Their research focuses on harnessing the immune system's ability to combat cancer cells. Targeting Macrophages to Control Cancer Growth Dr. Patnaik's team discovered that macrophages, a type of immune cell, play a crucial role in promoting the growth of prostate cancer. These macrophages express a molecule called PD-1, which suppresses the anti-cancer immune response. By targeting these macrophages, the researchers aimed to control the growth of the cancer. In a previous study, the team found that co-targeting the PI3K and PD-1 pathways enhanced the effects of hormonal therapy in PTEN-deficient prostate cancer, a particularly aggressive form of the disease. However, a significant portion of the mice remained resistant to this therapy. Further investigations revealed that the activation of the Wnt/β-catenin pathway restored lactate production in these treatment-resistant cancers, leading to macrophages promoting tumour growth. A Novel Therapeutic Approach Building on their previous findings, Dr. Patnaik and his team developed a novel therapeutic approach. By co-targeting the PI3K, MEK, and Wnt/β-catenin signalling pathways, they achieved an impressive 80% response rate in mouse models. However, a small percentage of the mice still showed resistance due to the restoration of lactate production in the treatment-resistant cancers. This led the researchers to investigate further and uncover the mechanism behind this resistance. They discovered that lactate can interact with macrophages and modify them through a process called histone lactylation, making the macrophages immunosuppressive and promoting cancer growth. In their latest study, the researchers found that targeting lactate as a macrophage phagocytic checkpoint can effectively control the growth of PTEN/p53-deficient prostate cancer. Through intermittent dosing of the three drugs, they achieved complete tumor control and significantly prolonged survival without the long-term toxicity associated with continuous drug administration. These groundbreaking findings provide "proof-of-concept" for a new treatment approach that holds great promise for the most aggressive forms of prostate cancer. The researchers believe that their strategy of harnessing the ability of macrophages to eliminate cancer cells could revolutionize cancer therapy. By flipping the switch in macrophages, the cancer cells can be effectively controlled and eliminated. The next step for Dr. Patnaik and his team is to translate these findings into clinical trials. They plan to develop a phase 1 clinical trial to test the efficacy of the intermittent dosing approach in human patients. If successful, this approach could potentially offer a new therapeutic option for patients with metastatic castrate-resistant prostate cancer, who currently have limited treatment options. The potential of this novel therapeutic approach extends beyond prostate cancer. The researchers have also uncovered new therapeutic opportunities by perturbing signaling pathways in cancer cells that affect the metabolic output of the cancer cell and its interaction with tumor-promoting macrophages. This opens up new avenues for research and the development of targeted therapies for various types of cancer. Conclusion The research conducted by Dr. Patnaik and his team has demonstrated the effectiveness of co-targeting multiple signaling pathways in treating aggressive forms of prostate cancer. Their findings provide a solid foundation for further investigation in human clinical trials and offer hope for patients with limited treatment options. This novel therapeutic approach has the potential to revolutionize cancer therapy and pave the way for more targeted and effective treatments in the future. Written by Sara Maria Majernikova Related article: A breakthrough drug discovery in cancer treatment References: Chaudagar, K., et al . (2023) Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis. Clinical Cancer Research . doi.org/10.1158/1078-0432.CCR-23-1441 Chetta, P., Sriram, R. and Zadra, G. (2023) ‘Lactate as key metabolite in prostate cancer progression: What are the clinical implications?’, Cancers , 15(13), p. 3473. doi: https://doi.org/10.3390/cancers15133473 . Mathieu (2023) Revolutionary breakthrough in prostate cancer treatment at the University of Bern , Greater Geneva Bern area . Available at: https://ggba.swiss/en/revolutionary-breakthrough-in-prostate-cancer-treatment-at-the-university-of-bern/(Accessed: 29 September 2023). Project Gallery

A disease of the blood Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Anaemia 09/07/25, 10:48 Last updated: Published: 17/06/23, 12:40 A disease of the blood This is article no. 1 in a series about anaemia. Next article: iron-deficiency anaemia Introduction Erythrocytes in their typical state are a biconcave and nucleus free cell responsible for carrying oxygen and carbon dioxide. The production is controlled by erythropoietin and as they mature in the bone marrow, they lose their nuclei. These red blood cells (RBC) contain haemoglobin, which aids in the transport of oxygen and iron, iron is a key component of haem, insufficient levels of iron leads to anaemic disorders. Low oxygen-carrying capacity may be defined by too few RBC in circulation or RBC dysfunction. Haem iron is acquired through the digestion of meat and transported through enterocytes of the duodenum, in its soluble form. Erythrocytic iron accounts for approximately 50% of the iron in blood. Metals cannot move freely throughout the body so they must be transported, the molecule involved in transporting iron is known as transferrin. Plasma transferrin saturation refers to the iron that is attached to transferrin, in iron deficient anaemia (IDA) this will always be low. Anaemia is physiological or pathological, these changes can be due to a plethora of causes; malabsorption due to diet or gastrointestinal (GI) conditions, genetic dispositions such as sideroblastic anaemias (SA), thalassaemia, or deficiency in erythropoietin due to comorbidities and chronic disease; where haemolysis is caused by autoimmune disorders, infections and drugs, or blood loss. Haem The iron is in a protoporphyrin ring at the centre of a haem molecule. The structure of haem consists of two alpha and two beta polypeptide chains to form a single haemoglobin macromolecule. Microcytic anaemias arise from problems in the creation of haemoglobin; sourcing through diet (IDA), synthesising protoporphyrin (SA) or from globin chain defects caused by thalassaemia. Summary Anaemia is a multifactorial condition with many different mechanisms involved, microcytic anaemias have an issue at the haemoglobin level, these can be acquired or inherited. A microcytic anaemia is caused by a failure to efficiently synthesise haemoglobin, whether from iron, protoporphyrin rings or globin chains. The diagnosis of anaemias is reliant on a patient’s background and medical history, as there are many factors involved in an anaemic disorder. A diagnosis should be patient led, as the age and sex of the patient can significantly highlight the origin and pathogenesis, as well as the prognosis and follow up care. Written by Lauren Kelly Related article: Blood Project Gallery