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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

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

Ways in which pathogens avoid being detected by the immune system Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Mechanisms of pathogen evasion 27/03/25, 11:23 Last updated: Published: 05/09/24, 10:54 Ways in which pathogens avoid being detected by the immune system Introduction Pathogens such as bacteria and viruses have evolved strategies to deceive and outsmart the immune system's defences. From hiding within cells to avoiding immune detection to blocking signals crucial for immune function, pathogens have developed an array of tactics to stay one step ahead of the immune system. This article introduces some key strategies pathogens employ to evade the immune system. Antigenic variation The influenza virus is a persistent and challenging pathogen to treat because it employs a clever strategy known as antigenic variation to evade the immune system. Antigenic variation is the pathogen’s ability to alter the proteins on its surface (antigens), particularly hemagglutinin (HA) and neuraminidase (NA), which are the primary targets of the immune system. As the virus conceals itself, it is no longer recognised and attacked by the host's defences. But how do the surface antigens change? This occurs through two primary mechanisms: antigenic drift and antigenic shift. The former process involves gradual changes in the virus's surface proteins by progressive accumulation of genetic mutations. Meanwhile, the latter requires a slightly different explanation. Antigenic shift is an abrupt process. It occurs when two influenza virus strains infect the same host cell and exchange genetic material. The exchange can lead to a new hybrid strain. This hybrid strain usually presents a new combination of surface proteins. It is a more abrupt process, and because the immune system lacks prior exposure to these new proteins, it fails to clear the viral pathogen. Antigenic shifts can lead to the emergence of strains to which the population has little to no pre-existing immunity. Some examples are the 1968 Hong Kong flu and the 2009 swine flu pandemic. Variable serotypes- Streptococcus pneumoniae When the host encounters a pathogen, the body creates antibodies against specific proteins on the pathogen's surface, ensuring long-term immunity. However, some species of pathogens evade this protection by evolving different strains. These strains involve multiple serotypes, each defined by distinct variations in the structure of their capsular polysaccharides. This variability allows them to infect the same host repeatedly, as immunity to one serotype does not confer protection against other serotypes. A perfect example of such a pathogen is the pneumonia-causing bacterium, Streptococcus pneumoniae , which has more than 90 strains. After successful infection with a particular S. pneumoniae serotype, a person will have devised antibodies that prevent reinfection with that specific serotype. However, these antibodies do not prevent an initial infection with another serotype, as illustrated in Figure 1 . Therefore, by evading the immune response, a new primary immune response is required to clear the infection. Latency- chicken pox & Human Immunodeficiency Virus (HIV) Pathogens can cleverly persist in the host by entering a dormant state where they are metabolically inactive. In this state, they are invisible to the immune system. Human Immunodeficiency Virus is well known for its use of HIV latent reservoirs. These reservoirs, consisting of metabolically inactive T-cells infected with HIV, can exist for years on end. When the host becomes immunocompromised at any stage in life, the T-cells in these reservoirs are suddenly activated to renew HIV production. The Varicella-Zoster Virus (VZV) is responsible for causing varicella (chickenpox) and zoster (shingles). Similarly, this virus can remain latent in the host to evade immune detection. VZV establishes latency in sensory ganglia, particularly in neurons. Since neurons are relatively immune-privileged sites, they are less accessible to immune surveillance mechanisms. This provides a safe haven from immune detection. When the host is immunocompromised, the virus reactivates. This renewed viral activity results in the production of viral particles which travel along the sensory nerve fibres towards mucous membranes. When the virus reaches the skin, it causes an inflammatory response. This results in painful vesicular skin lesions, commonly known as shingles (herpes zoster). Conclusion Pathogens employ diverse mechanisms to evade the host immune system, ensuring their survival and propagation through host cells. These evasion mechanisms can hinder the development of treatments for certain infectious diseases. For instance, the diversity in Strep A serotypes challenges vaccine development because immunity to one serotype may not confer protection against another. Additionally, the influenza virus constantly evolves via antigenic variation, always one step ahead of the immune system. The strategies employed by pathogens to evade the immune system are as diverse as they are sophisticated. Scientists continue to study these mechanisms, paving the way for developing more effective vaccines, treatments, and public health strategies to out-manoeuvre these organisms. We can better protect human health by staying one step ahead of pathogen evolution. Written by Fozia Hassan Related articles: Allergies / Plant diseases REFERENCES Abendroth, Allison, et al. “Varicella Zoster Virus Immune Evasion Strategies.” Current Topics in Microbiology and Immunology , 2010, pp. 155–171, www.ncbi.nlm.nih.gov/pmc/articles/PMC3936337/ , https://doi.org/10.1007/82_2010_41 . Accessed 24 July 2024. Gougeon, M-L. “To Kill or Be Killed: How HIV Exhausts the Immune System.” Cell Death & Differentiation , vol. 12, no. S1, 15 Apr. 2005, pp. 845–854, www.nature.com/articles/4401616 , https://doi.org/10.1038/sj.cdd.4401616 . Accessed 24 July 2024. Parham, Peter. The Immune System . 5th ed., New York, Garland Science, 2015, read.kortext.com/reader/epub/1743564 . Accessed 24 July 2024. Shaffer, Catherine. “How HIV Evades the Immune System.” News-Medical.net , 21 Feb. 2018, www.news-medical.net/life-sciences/How-HIV-Evades-the-Immune-System.aspx . Accessed 24 July 2024. Project Gallery

Exploring the distinctive features that define and disrupt the brain Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A deep dive into the hallmarks defining Alzheimer’s disease 08/07/25, 14:39 Last updated: Published: 06/11/24, 12:02 Exploring the distinctive features that define and disrupt the brain The progressive decline in neurocognition, resulting in a detrimental effect on one’s activities of daily living, is referred to as dementia. It typically affects people over the age of 65. Multiple theories have been proposed to explain the pathogenesis of Alzheimer’s disease (AD), including the buildup of amyloid plaques in the brain and the formation of neurofibrillary tangles (NFT) in cells. Understanding the pathophysiology of AD is imperative to the development of therapeutic strategies. Therefore, this article will outline the major hallmarks and mechanisms of AD. Hallmark 1: amyloid plaques One of the most widely accepted hypotheses for AD is the accumulation of amyloid beta protein (Aβ) in the brain. Aβ is a 4.2 kDa peptide consisting of approximately 40–42 amino acids, originating from a precursor molecule called amyloid precursor protein. This process, defined as amyloidosis, is strongly linked to brain aging and neurocognitive decline. How do the amyloid plaques form? See Figure 1 . Reasons for the accumulation of amyloid plaques: Decreased autophagy: Amyloid proteins are abnormally folded proteins. Autophagy in the brain is primarily carried out by neuronal and glial cells, involving key structures known as autophagosomes and lysosomes. When autophagy becomes downregulated, the metabolism of Aβ is impaired, eventually resulting in plaque buildup. Overproduction of acetylcholinesterase (AChE): Acetylcholine (Ach) is the primary neurotransmitter involved in memory, awareness, and learning. Overproduction of ACHE by astrocytes into the synaptic cleft can lead to excessive breakdown of Ach, with detrimental effects on cognition. Reduced brain perfusion: Blood flow delivers necessary nutrients and oxygen for cellular function. Reduced perfusion can lead to “intracerebral starvation”, depriving cells of the energy needed to clear Aβ. Reduced expression of low-density lipoprotein receptor-related protein 1: Low-density lipoprotein receptor-related protein 1 (LRP1) receptors are abundant in the central nervous system under normal conditions. They are involved in speeding up the metabolic pathway of Aβ by binding to its precursor and transporting them from the central nervous system into the blood, thereby reducing buildup. Reduced LRP1 expression can hinder this process, leading to amyloid buildup. Increased expression of the receptor for advanced glycation end products (RAGE): RAGE is expressed on the endothelial cells of the BBB, and its interaction with Aβ facilitates the entry of Aβ into the brain. Hallmark 2: neurofibrillary tangles See Figure 2 Neurofibrillary tangles are excessive accumulations of tau protein. Microtubules typically support neurons by guiding nutrients from the soma (cell body) to the axons. Furthermore, tau proteins stabilise these microtubules. In AD, signalling pathways involving phosphorylation and dephosphorylation cause tau proteins to detach from microtubules and stick to each other, eventually forming tangles. This results in a disruption in synaptic communication of action potentials. However, the exact mechanism remains unclear. Recent studies suggest an interaction between Aβ and tau, where Aβ can cause tau to misfold and aggregate, forming neurofibrillary tangles inside brain cells. Both Aβ and tau can self-propagate, spreading their toxic effects throughout the brain. This creates a vicious cycle, where Aβ promotes tau toxicity, and toxic tau can further exacerbate the harmful effects of Aβ, ultimately causing significant damage to synapses and neurons in AD. Hallmark 3: neuroinflammation Microglia are the primary phagocytes in the central nervous system. They can be activated by dead cells and protein plaques, where they initiate the innate immune response. This involves the release of chemokines to attract other white blood cells and the activation of the complement system which is a group of proteins involved in initiating inflammatory pathways to fight pathogens. In AD, microglia bind to Aβ via various receptors. Due to the substantial accumulation of Aβ, microglia are chronically activated, leading to sustained immune responses and neuroinflammation. Conclusion The contributions of amyloid beta plaques, neurofibrillary tangles and chronic neuroinflammation provide a framework for understanding the pathophysiology of AD. AD is a highly complex condition with unclear mechanisms. This calls for the need of continued research in the area as it is crucial for the development of effective treatments. Written by Blessing Amo-Konadu Related articles: Alzheimer's disease (an overview) / CRISPR-Cas9 to potentially treat AD / Sleep and memory loss REFERENCES 2024 Alzheimer’s Disease Facts and Figures. (2024). Alzheimer’s & dementia, 20(5). doi:https://doi.org/10.1002/alz.13809. A, C., Travers, P., Walport, M. and Shlomchik, M.J. (2001). The complement system and innate immunity. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK27100/ . Bloom, G.S. (2014). Amyloid-β and tau: the Trigger and Bullet in Alzheimer Disease Pathogenesis. JAMA neurology, [online] 71(4), pp.505–8. doi:https://doi.org/10.1001/jamaneurol.2013.5847. Braithwaite, S.P., Stock, J.B., Lombroso, P.J. and Nairn, A.C. (2012). Protein Phosphatases and Alzheimer’s Disease. Progress in molecular biology and translational science, [online] 106, pp.343–379. doi:https://doi.org/10.1016/B978-0-12-396456-4.00012-2. Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., Jacobs, A.H., Wyss-Coray, T., Vitorica, J., Ransohoff, R.M., Herrup, K., Frautschy, S.A., Finsen, B., Brown, G.C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A. and Petzold, G.C. (2015). Neuroinflammation in Alzheimer’s disease. The Lancet. Neurology, 14(4), pp.388–405. doi:https://doi.org/10.1016/S1474-4422(15)70016-5. Kempf, S. and Metaxas, A. (2016). Neurofibrillary Tangles in Alzheimer′s disease: Elucidation of the Molecular Mechanism by Immunohistochemistry and Tau Protein phospho- proteomics. Neural Regeneration Research, 11(10), p.1579. doi:https://doi.org/10.4103/1673-5374.193234. Kumar, A., Tsao, J.W., Sidhu, J. and Goyal, A. (2022). Alzheimer disease. [online] National Library of Medicine. Available at: https://www.ncbi.nlm.nih.gov/books/NBK499922/. Ma, C., Hong, F. and Yang, S. (2022). Amyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules, 27(4), p.1210. doi:https://doi.org/10.3390/molecules27041210. National Institute on Aging (2024). What Happens to the Brain in Alzheimer’s Disease? [online] National Institute on Aging. Available at: https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain- alzheimers-disease. Stavoe, A.K.H. and Holzbaur, E.L.F. (2019). Autophagy in Neurons. Annual Review of Cell and Developmental Biology, 35(1), pp.477–500. doi: https://doi.org/10.1146/annurev-cellbio-100818-125242 . Project Gallery