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

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

Molecular gastronomy Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring food at a molecular level 09/07/25, 14:07 Last updated: Published: 13/05/24, 14:46 Molecular gastronomy Imagine taking a bite of your favourite dish, not just savouring the flavours, but peering into the very essence of its existence. That's the realm of molecular gastronomy, a fascinating exploration of food through the lens of science. This article takes you on a journey at the microscopic level of what fuels the human body. The foundation of all food lies in macromolecules, large molecules formed from the intricate assembly of smaller ones. Carbohydrates, proteins, and lipids are the main players, each with unique structures and roles. Carbohydrates: These sugary giants, like starches and sugars, provide our bodies with energy. Imagine them as long chains of sugar molecules linked together, like beads on a necklace. Proteins: The workhorses of the cellular world, proteins are responsible for countless functions. They're built from amino acids, each with a distinct side chain, creating a diverse and essential cast of characters. Lipids: Fats and oils, these slippery molecules store energy and form cell membranes. Think of them as greasy chains with attached rings, like chubby tadpoles swimming in oil. The symphony of cooking and the final dance Applying heat, pressure, and chemical reactions, chefs become culinary alchemists at the molecular level. Water, the universal solvent, facilitates the movement and interaction of these molecules. As we cook, proteins unfold and rearrange, starches break into sugars, and fats melt and release flavours. Maillard Reaction: This browning phenomenon, responsible for the delicious crust and crunch on your food, arises from the dance between sugars and amino acids. Imagine them waltzing and exchanging partners, creating new flavorful molecules that paint your food with golden hues. Emulsification: Oil and water don't mix, but lecithin, a molecule found in egg yolks, acts as a matchmaker. It bridges the gap between these unlikely partners, allowing for the creation of creamy sauces and fluffy cakes. Think of lecithin as a tiny cupid, shooting arrows of attraction between oil and water droplets. Saponification: Techniques like spherification use alginate and calcium to create edible spheres filled with liquid, transforming into playful pearls that burst with flavor in your mouth. A world of potential Understanding food at the molecular level unlocks a treasure trove of possibilities. It can help us create healthier, more sustainable food choices, develop personalized nutrition plans, and even combat food-borne illnesses. By peering into the microscopic world of our meals, we gain a deeper appreciation for the magic that happens on our plates, bite after delicious bite. So next time you savor a meal, remember the intricate dance of molecules that brought it to life. From the building blocks of carbohydrates to the symphony of cooking, food is a story written in the language of chemistry, waiting to be deciphered and enjoyed. Written by Navnidhi Sharma Related articles: Emotional chemistry on a molecular level / Food prices and malnutrition / Vitamins References and further readings: Chapter 2: Protein structure . (2019, July 10). Chemistry. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-d efining-life-at-the-molecular-level/chapter-2-protein-structure/ Gan, J., Siegel, J. B., & German, J. B. (2019). Molecular annotation of food - Towards personalized diet and precision health. Trends in Food Science & Technology , 91 , 675–680. https://doi.org/10.1016/j.tifs.2019.07.016 Grant, P. (2020, August 4). Sugar, fiber, starch: What’s A carbohydrate? — Pamela Grant, L.Ac , NTP. Pamela Grant, L.Ac , NTP . https://pamela-grant.com/blog-ss/sugar-fiber-starch Helmenstine, A. (2022, October 25). Examples of carbohydrates . Science Notes and Projects. https://sciencenotes.org/examples-of-carbohydrates/ Project Gallery

What they are, uses, and future outlook Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Advancements in Semiconductor Laser Technology 08/07/25, 16:19 Last updated: Published: 23/06/24, 09:39 What they are, uses, and future outlook Lasers have revolutionised many fields starting from the telecommunications, data storage to medical diagnostics and consumer electronics. And among the semiconductor laser technologies, Edge Emitting Lasers (EEL) and Vertical Cavity Surface Emitting Lasers (VCSEL) emerged as critical components due to their unique properties and performance. These lasers generate light through the recombination of electrons and holes in a semiconductor material. EELs are known for their high power and efficiency and they are extensively used in fiber optic communications and laser printing. VCSELs on the other hand are compact and are used for applications like 3D sensing. Traditionally VCSELs have struggled to match the efficiency levels of EELs however a recent breakthrough particularly in multi junction VCSEL, has demonstrated remarkable efficiency improvements which place the VCSELs to surpass EELs in various applications. This article focuses on the basics of these laser technologies and their recent advancements. EELs are a type of laser where light is emitted from the edge of the semiconductor wafer. This design contrasts with the VCSELs which emit light perpendicular to the wafer surface. EELs are known for their high power output and efficiency which makes them particularly suitable for applications that require long-distance light transmission such as fiber optic communications, laser printing and industrial machining. EELs consist of an active region where electron hole recombination occurs to produce light. This region is sandwiched between two mirrors forming a resonant optical cavity. The emitted light travels parallel to the plane of the semiconductor layers and exits from the edge of the device. This design allows EELs to achieve high gain and power output which makes them effective for transmitting light over long distances with minimal loss. VCSELs are a type of semiconductor laser that emits light perpendicular to the surface of the semiconductor wafer unlike the EELs which emit light from the edge. VCSELs have gained popularity due to their lower threshold currents and ability to form high density arrays. VCSELs consist of an active region where electron-hole recombination occurs to produce light. This region is situated between two highly reflective mirrors which forms a vertical resonant optical cavity. The light is emitted perpendicular to the wafer surface which allows for efficient vertical emission and easy integration into arrays. Recent advancements in VCSEL technology marked a significant milestone in the field of semiconductor lasers. And in particular the development of multi junction VCSEL which led to the improvements in power conversion efficiency (PCE) of the laser. Research conducted by Yao Xiao et al. and team has demonstrated the potential of a multi junction VCSELs to achieve efficiency levels which were previously thought unattainable. This research focuses on cascading multiple active regions within a single VCSEL to enhance gain and reduce threshold current which leads to higher overall efficiency. The study employed a multi-junction design where several active regions are stacked vertically within the VCSEL. This design increases the volume of the gain region and lowers the threshold current density resulting in higher efficiency. Experimental results from the study revealed that a 15-junction VCSEL achieved a PCE of 74% at room temperature when driven by nanosecond pulses. This efficiency is the highest ever reported for VCSELs and represents a significant leap forward from previous records. Simulations conducted as part of the study indicated that a 20-junction VCSEL could potentially reach a PCE exceeding 88% at room temperature. This suggests that further optimization and refinement of the multi-junction approach could yield even greater efficiencies. The implications of this research are profound for the future of VCSEL technology. Achieving such high efficiencies places VCSELs as strong competitors to EELs particularly in applications where energy efficiency and power density are critical. The multi junction VCSELs demonstrated in the study shows promise for a wide range of applications and future works may focus on optimizing the fabrication process, reducing thermal management issues and exploring new materials to further enhance performance. Integrating these high-efficiency VCSELs into commercial products could revolutionize industries reliant on laser technology. Written by Arun Sreeraj Related articles: The future of semi-conductor manufacturing / The search for a room-temperature superconductor / Advances in mass spectrometry Project Gallery

An overview Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Epithelioid hemangioendothelioma (EHE) 09/07/25, 14:05 Last updated: Published: 25/02/24, 14:52 An overview This is article no. 4 in a series on rare diseases. Next article: Unfolding prion disease . Previous article: Herpes vs devastating skin disease . Gene fusion and EHE Epithelioid hemangioendothelioma (EHE) is a rare cancer which arises from the cells lining the blood vessels (endothelial cells). This occurs when two genes fuse together. Generally, there are several different gene fusions which lead to cancer, predominantly in prostate, ovarian, blood, and sarcomas (soft tissue cancer). These arise from two genes which bind together to create a fusion oncogene, such as the classical example of the BCR-ABL1 fusion gene, called the “Philadelphia chromosome,” in chronic myeloid leukaemia . EHE is a rare vascular sarcoma caused by a fusion between two genes, primarily TAZ and CAMTA1. TAZ is part of the Hippo signalling pathway (see below) and is a transcriptional co-activator (it binds to a transcription factor to activate the first step in gene expression, which is the conversion of DNA to RNA). Less is known about CAMTA1, although it is a transcription activator found primarily in the brain. However, there are also a small number of cases (10%) caused by a YAP1-TFE3 fusion. YAP1 is also part of the Hippo pathway, whilst TFE3 is a transcription factor. EHE is a prime example of the importance of gene fusions (and other chromosomal rearrangements) in the genetic origin of many cancers. Therefore, further understanding of this disease may provide clues into the tumourigenesis of other different cancers. EHE is extremely rare at a prevalence of 1 in 1 million and presents more often in females, but it can occur in either sex at any age. It is most common in the liver and lung and has an unusual pathology, as it can present as an aggressive or indolent (slow-growing) cancer. Similarly to many cancers, symptoms can present as any or all the following: a mass, fever, fatigue, pain, and weight loss. It may also have no symptoms and be highlighted by chance whilst undergoing other investigations. Cellular signalling behind EHE: the Hippo pathway The Hippo pathway controls tissue growth and is the signalling mechanism behind EHE. YAP/TAZ are vital members of this pathway and are oncogenic transcription (co-) factors in many solid tumours. They have also been shown to be crucial for cancer initiation, progression, and metastasis. However, surprisingly, certain blood cancers, such as leukaemia, myeloma, and lymphoma, show reduced levels of YAP/TAZ. Therefore, it seems YAP/TAZ behave differently depending on cell type. High expression of YAP/TAZ (or nuclear localization) is related to poor prognosis in breast, colorectal, liver, lung, gastric, pancreatic, ovarian, endometrial, oesophageal, and bladder cancers. YAP/TAZ are phosphorylated and degraded in the cytoplasm when the Hippo pathway is ‘on.’ However, when the Hippo pathway is ‘off,’ YAP/TAZ move to the nucleus, where they are involved in transcription (see the signalling pathway diagram). However, in EHE disease, even when Hippo is ‘on,’ TAZ-CAMTA1/YAP1-TFE3 override this and move to the nucleus to be involved in aberrant (atypical) transcription. YAP/TAZ bind to TEAD ( DNA-binding domain ) in the nucleus, whilst CAMTA1 and TFE3 are thought to be involved in chromatin remodelling. Chromatin consists of tightly packed DNA and histones (proteins). Chromatin remodelling results in the chromatin unwinding and the DNA becoming more accessible for transcription (i.e. ‘switching on’ certain genes). Therefore, this may lead to overexpression and subsequently, cancer. EHE treatment There are no standard treatments for EHE, but indolent cancers are often treated by monitoring, a ‘watch-and-wait’ strategy. Surgery is a common form of treatment for single tumours. Ablation (burning/freezing), isolated limb perfusion (drug treatment to one limb), vascular embolization (blocking tumour blood supply), and radiation therapy are also other forms of possible treatment, along with the mammalian target of rapamycin (mTOR) inhibitors (the mTOR pathway controls cell proliferation/metabolism). Tyrosine kinase inhibitors (tyrosine kinases activate proteins in related pathways) and interferon (immune system modulators) are two other possible treatments. A transplant could also be an option if there is an organ with multiple tumours (most often the liver). However, more effective treatments are needed and research into this disease is currently underway. Summary EHE is a rare cancer which arises from the cells lining the blood vessels. It occurs from gene fusions, primarily TAZ-CAMTA1. TAZ is part of the Hippo signalling pathway, which controls tissue growth. Therefore, Hippo is a vital pathway involved in many cancers, and understanding this pathway in EHE disease may provide clues as to the tumourigenesis of other cancers. Written by Eleanor R. Markham Related articles: The Hippo signalling pathway / Apocrine carcinoma (a rare form of breast cancer) Project Gallery

Landing on the moon (again!) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Artemis: the Lunar South Pole Base 09/07/25, 10:55 Last updated: Published: 13/01/24, 15:44 Landing on the moon (again!) Humans have not visited the moon since 1972, but that’s about to change. Thanks to NASA’s Artemis missions, we have already taken the first small step towards our own lunar home for astronauts. NASA has established the second generation of its lunar missions- “Artemis”, fittingly named after the ancient Greek Goddess of the Moon, and Apollo’s twin. The ultimate aim of the Artemis missions is to solidify a stepping stone to Mars. Technologies will be developed, tested, and perfected, before confidence is built to travel on to Mars. NASA has to consider the natural conditions of the Moon, since doing so will allow astronauts to limit their reliance on resources from Earth, and increase their length of stay and therefore potential for research. The amount achieved would be extremely limited if a lunar mission relied solely on resources from Earth, due to the limitation of rocket payloads. This is known as In-Situ Resource Utilisation, and in addition to extended lunar stays, its success on the Moon is essential if we hope to one day establish a base on Mars. As a priority, astronauts need to have access to energy and water. Luckily, the conditions at the lunar south pole may be ideal for this. Unlike Earth, where we experience seasons due to its 23.5° tilt, the Moon’s tilt is tiny, at only 1.5°. This means some areas at the lunar poles are almost always exposed to sunlight, providing a reliable source of solar energy generation for a potential Artemis Base Camp. And since the Sun is always near the horizon at the poles, there are even areas in deep craters that never see the light. These areas of “eternal darkness” can reach temperatures of -235°, possibly allowing astronauts access to water ice. Aside from access to resources, Artemis has to consider the dangers that come from living in space. Away from the safety of Earth’s protective atmosphere and magnetosphere, astronauts would be exposed to harsh solar winds and cosmic rays. To combat this, NASA hopes to make use of the terrain surrounding the base, highlighting another advantage of the hilly south pole [3]. The exact location for the Artemis Base is currently undecided. We just know it will most likely be near a crater rim by the south pole, and on the Earth-facing side to allow for communication to and from Earth. Not only is the south pole ideal from a practical standpoint, it is also an area of exciting scientific interest. Scientists will have access to the South Pole–Aitken basin, not only the oldest and largest confirmed impact crater on the Moon, but the second largest confirmed impact crater in the entire Solar System. With a depth of up to 8.2 km, and diameter of 2500 km, it is thought this huge crater will contain exposed areas of lower crust and mantle, providing an insight into the Moon’s history and formation. Additionally, thanks to areas of “eternal darkness” the ice water found deep within craters at the south pole may hold trapped volatiles up to 3.94 billion years old, which, although not as ancient as previously expected, can still provide an insight into the evolution of the Moon. The scientific potential of the Artemis Base Camp extends far beyond location specific investigations to our most fundamental understanding of physics, from Quantum Physics to General Relativity. Not to mention the astronauts themselves, as well as “model organisms” which will be the focus of physiological studies into the effects of extreme space environments. Artemis Timeline Overview Artemis 1 launched on 16th November 2022. It successfully tested the use of two key elements of the Artemis mission- Orion and the Space Launch System (SLS)- with an orbit around the moon. Orion, named after the Goddess Artemis' hunting partner, is the spacecraft that will carry the Artemis crew into lunar orbit. It is carried by the SLS, NASA’s super heavy-lift rocket, one of the most powerful rockets in the world. Artemis 2 plans to launch late 2024 and will be the first crewed Artemis mission, with a lunar flyby bringing four astronauts further than humans have ever travelled beyond Earth. Artemis 3 plans to launch the following year. It will be the historic moment that will see humans step foot on the surface of the moon for the first time since we left in 1972. The mission will be the first use of another key element of the Artemis missions- the Human Landing System (HLS). Astronauts will use a lunar version of SpaceX’s Starship rocket as the HLS for Artemis 3 and 4. (Starship is currently in its test stage, with its second test launch carried out very recently on the 18th November 2023.) Two astronauts will stay on the lunar surface for about a week, beating the current record of 75 hours on the Moon by Apollo 17. Artemis 4 plans to launch in 2028. The mission will include the first use of Gateway, another key element to the Artemis missions. Gateway will be a multifunctional lunar space station, designed to transfer astronauts between Orion and HLS, as well as hosting astronauts to live and research in lunar orbit. Gateway will be constructed over Artemis 4-6 , with each mission completing an additional module. NASA plans to have Artemis missions extending for years beyond this, with over 10 proposed and more expected. Eventually we will have a working base on the Moon with astronauts able to stay for months at a time. Having already started a year ago, Artemis will continue to expand our horizons. We can look forward to uncovering long held secrets of the Moon, and soon, setting our sights confidently on Mars. Written by Imo Bell Related articles: Exploring Mercury / Fuel for the colonisation of Mars / Nuclear fusion REFERENCES How could we live on the Moon? - Institute of Physics. Available at: https://www.iop.org/explore-physics/moon/how-could-we-live-on-the-moon Understanding Physical Sciences on the Moon - NASA. Available at: https://science.nasa.gov/lunar-science/focus-areas/understanding-physical-sciences-on-themoon NASA’s Artemis Base Camp on the moon will need light, water, elevation - NASA. Available at: https://www.nasa.gov/humans-in-space/nasas-artemis-base-camp-on-the-moon-will-need-ligh t-water-elevation Zuber, M.T. et al. (1994) ‘The shape and internal structure of the Moon from the Clementine Mission’, Science, 266(5192), pp. 1839–1843. doi:10.1126/science.266.5192.1839. Flahaut, J. et al. (2020) ‘Regions of interest (ROI) for future exploration missions to the Lunar South Pole’, Planetary and Space Science, 180, p. 104750. doi:10.1016/j.pss.2019.104750. Moriarty, D.P. et al. (2021) ‘The search for lunar mantle rocks exposed on the surface of the Moon’, Nature Communications, 12(1). doi:10.1038/s41467-021-24626-3. Estimates of water ice on the Moon get a ‘dramatic’ downgrade - Physics World. Available at: https://physicsworld.com/a/estimates-of-water-ice-on-the-moon-get-a-dramatic-downgrade Biological Systems in the lunar environment - NASA. Available at: https://science.nasa.gov/lunar-science/focus-areas/biological-systems-in-the-lunar-environme Https://www.nasa.gov/wp-content/uploads/static/artemis/NASA : Artemis - NASA. Available at: https://www.nasa.gov/specials/artemis Project Gallery

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

The importance of implementing Maths into our lives Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Teaching maths like it matters 11/07/25, 09:54 Last updated: Published: 03/10/23, 13:43 The importance of implementing Maths into our lives …But I’m never going to use Algebra in my life! The above is a typical response from students across the country when walking into a Maths class. I did not understand others’ disdain, because I love Maths. I got satisfaction from solving numerical problems, stimulation from equations, and excitement from learning new variables like alpha, or constants like Pi. The abstract nature of Maths was like art to me. Later, I realised that not all my peers felt the same way, that somehow, I was the anomaly and that they were the norm. Many maths teachers feel the same way. They get lost in the subject that they love and try to teach it in the way that makes sense to them, without thinking on how the lack of context in equations and processes means nothing to disengaged students. As teachers, our job is to show how applicable Maths can be to our students on an individual basis. Rather than using real-life questions as extensions after the core activity, we must utilise them from the beginning when introducing topics, showing student’s how the methods that they learn can be applied to have some use beyond a pass mark in their exams. I am not talking about examples of ladders leaning against walls when teaching Pythagoras’ theorem and SOHCAHTOA, or, taking counters from a bag, to explain Probability. The examples here are forced, no student will connect with them because they are not lived examples or likely scenarios in most of their lives. We need to build strong relationships with our students, understand their demographic and interests, then introduce topics based on this. For example: If I know that my class enjoys football, I will begin with a video of Messi playing the game, pausing the video, and splitting the pitch up into segments, which can lead a conversation into areas of segments and circles, or, I can discuss the trajectory of the ball after a kick, to talk about quadratic equations. In another class, we can ask what students are budgeting for, perhaps concert tickets or new clothes, and use that to open a discussion into arithmetic series. Another great example is asking students to find an event happening somewhere in the country that they would like to go to, and as a class, plan for this. We would use research skills, calculate speed, distance and time if going by car, or pull up a train timetable where we can teach two-way tables and time conversions. To create meaningful connections to Math topics will take time, effort, and research, and the difficulty will be that not every application will be relatable to every cohort. We will need to build a portfolio of contextual examples related to each topic, however, if there is buy-in from others in our departments, it is an achievable target. In conclusion, we must teach Maths to students in meaningful ways that applies to their life, to keep up engagement and motivation as well as providing opportunities to deepen understanding. Maths should be based around conversation and interests, rather than an exercise of memorising and processes. It should make sense to students, it should matter. Written by Sara Altaf Related article: The game of life Project Gallery

Navigating the silence Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unveiling the underreported challenges of endometriosis 14/07/25, 15:10 Last updated: Published: 25/11/23, 11:22 Navigating the silence What is endometriosis? Endometriosis is a chronic, neuro-inflammatory disease that affects 1 in 10 women in the UK. It is associated with debilitating chronic pelvic pain caused by tissue alike the lining of the womb (uterus) grows outside the uterus in other places like the ovaries and fallopian tubes. Endometriosis can affect any woman of reproductive age with a lifelong impact and can even lead to infertility. During a normal menstrual cycle, the body undergoes monthly hormonal changes. Natural hormonal release causes the uterus lining to thicken in preparation of a fertilised egg. If there is no pregnancy, the uterus lining will break down and bleed and is then released from the body in the form of a period. In endometriosis, tissue alike to the uterus lining tissue behaves in the same way the uterus tissue behaves every month during the menstrual period: building up, breaking down then bleeding. Unlike the womb tissue broken down blood, this blood has no way to leave. The internal bleeding causes inflammation, debilitating pain, and scar tissue formation. The symptoms are: · Painful, heavy, long periods · Infertility · Pain during or after sex · Painful bowel movements · Mood disorders like anxiety or depression · Chronic fatigue · Chronic pelvic pain The challenges of endometriosis Contrary to popular belief, period pain is not normal and can be experienced by those without endometriosis. The main point is if your period pain is interfering with your daily life, please consult your doctor. There are many challenges behind endometriosis from the hard time a patient has to get a diagnosis, to the severely under-research of the condition. Unfortunately, since endometriosis shares symptoms with many other conditions, diagnosis can be delayed and strenuous with recent research showing the average time to get a firm diagnosis being 7.5 years. A 2021 focus group in the Netherlands also shows the many issues with diagnosing endometriosis. Many of the focus group reported having a hard time finding a doctor who does not dismiss their concerns, undermine their pain, or dismiss them with paracetamol or ibuprofen which patients have reported as not strong for the pain endometriosis causes. Little research has been done on how effective paracetamol or ibuprofen is with endometriosis pain, but anecdotal evidence suggests it is not effective. Many of them reported their concerns being unheard, told to come back when they want to have a child and that their pain is normal, so they don’t need to see a doctor. Research for endometriosis is heavily underfunded, women reproductive health disorders are generally underfunded. There is a huge gender disparity with disorders that mostly affect men being over-funded while disorders affecting mostly women being underfunded. A 2018 analysis by the UK Clinical Research Collaboration reported findings of only 2.1% of public funded medical research going towards childbirth and reproductive health which is down from 2.5% in 2014. A 16% funding decrease over a 4-year period. The UK Research and Innovation (UKRI) has funded just over 40 endometriosis-related projects since 2003. However, diabetes which has the same incident rate but affecting both sexes instead of one like endometriosis has been funded 1891 projects in the same time. Just over 1m was funded to 6 of the endometriosis projects compared almost 250 diabetes projected with more than 10 receiving funding greater than £10 million. In 2020 the UK’s All-Part Parliament Group (APPG) report on Endometriosis calls the attention of the cause of the disorder being unclear: Historically, with limited investment in research into women’s health in general, there’s been so little investment in research into endometriosis that we don’t even know what causes it, and without knowing the cause, a cure cannot be found. - APPG The APPG called for more investment into the cause, diagnosis, treatment, and management options of endometriosis. Without investment in research, this condition will rob the next generation of women [of] the education, care, and support they deserve. – APPG With more awareness being brought up by endometriosis charities, researchers and the affected group, the hard work and motivation may pay off soon. Written by Blessing O. Related articles: Breakthrough in endometriosis treatment / Gynaecology Project Gallery