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Nuclear medicine Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Physics in healthcare 10/07/25, 10:28 Last updated: Published: 06/01/24, 10:47 Nuclear medicine When thinking about a career or what to study in university, many students interested in science think that they have to decide between a more academic route or something more vocational, such as medicine. Whilst both paths are highly rewarding, it is possible to mix the two. An example of this is nuclear medicine, allowing physics students to become healthcare professionals. Nuclear medicine is an area of healthcare that involves introducing a radioactive isotope into the system of a patient in order to image their body. A radioactive isotope is an unstable nucleus that decays and emits radiation. This radiation can then be detected, usually by a tool known as a gamma camera. It sounds dangerous, however it is a fantastic tool that allows us to identify abnormalities, view organs in motion and even prevent further spreading of tumours. So, how does the patient receive the isotope? It depends on the scan they are having! The most common route is injection but it is also possible for the patient to inhale or swallow the isotope. Some hospitals give radioactive scrambled eggs or porridge to the patient in gastric emptying imaging. The radioisotope needs to obey some conditions: ● It must have a reasonable half-life. The half-life is the time it takes for the isotope to decay to half of the original activity. If the half-life is too short, the scan will be useless as nothing will be seen. If it is too long, the patient will be radioactive and spread radiation into their immediate surroundings for a long period of time. ● The isotope must be non-toxic. It cannot harm the patient! ● It must be able to biologically attach to the area of the body that is being investigated. If we want to look at bones, there is no point in giving the patient an isotope that goes straight to the stomach. ● It must have radiation of suitable energy. The radiation must be picked up by the cameras and they will be designed to be most efficient over a specific energy range. For gamma cameras, this is around 100-200 keV. Physicists are absolutely essential in nuclear medicine. They have to understand the properties of radiation, run daily quality checks to ensure the scanners are working, they must calibrate devices so that the correct activity of radiation is being given to patients and so much more. It is essential that the safety of patients and healthcare professionals is the first priority when it comes to radiation. With the right people on the job, safety and understanding is the priority of daily tasks. Nuclear medicine is indeed effective and is implemented into standard medicine thanks to the work of physicists. Written by Megan Martin Related articles: Nuclear fusion / The silent protectors / Radiotherapy Project Gallery

Pisaster ochraceus (also known as ‘ochre stars’) is a keystone species and common starfish found in the Pacific Ocean and are very interesting species to research on. They are found mainly in Alaska and Baja California. Their size range from 15 to 36cm in diameter come in different ranges of colours eg: red, yellow, orange and purple. Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Designing an experiment on sea stars Last updated: 17/11/24 Published: 25/03/23 Title: How do light and dark rocky surfaces affect the relative fitness of the orange and purple ochre stars? Pisaster ochraceus (also known as ‘ochre stars’) is a keystone species and common starfish found in the Pacific Ocean and are very interesting species to research on. They are found mainly in Alaska and Baja California. Their size range from 15 to 36cm in diameter come in different ranges of colours eg: red, yellow, orange and purple. They are mainly found near rocky shores and found under rocks and in crevices in the low and intertidal zones and they often cluster together. They are simple organisms, they do not have brain or ganglia and around its mouth there is a nerve ring which connects with 5 radial nerves. The population of Pisaster ochraceus that are orange are 6- 28%, whilst majority are purple and researchers have seen that mainly genetic traits cause these species to have different colours whilst they develop. There have also been experiments that examined how colour changes across the geographic range. Figure 1: Image of purple and orange ochre stars The aim of the experiment would be to see how either light or dark rocky surfaces affect the relative fitness of the orange and purple ochre stars, meaning their offspring. The relative fitness shows how much fitness there is in a genotype compared to the maximum fitness. Before starting this experiment, a risk assessment has to be done to make sure it is safe and increases hazard awareness when the experiment is being done. The likelihood, severity and risk has to be looked into during the assessment and how to reduce the risk. One example is, doing the experiment by the shores can be risky due to wind waves and tides and so appropriate footwear has to be worn and the weather should be looked into before going to do this experiment. There are going to be control variables such as: season, quadrat area, number of samples calculated and same equipment being used throughout the whole day so validity would be affected. The uncontrolled variables would be: temperature, pH of seawater and predators that consume Pisaster ochraceus . In order to see how the Pisaster ochraceus are affected, 10 - 15 sites should be chosen and a quadrat can be used (10 metres by 10 metres) on each site and running parallel by using a tape measure on darker rocky surfaces and then after on lighter rocky surfaces. This will be useful as you can see the distribution. Place 15 quadrats randomly over each area in every site to work out the abundance. Within each quadrat, orange and purple Pisaster ochraceus are counted separately to illustrate the set of results with the different colours and the rocky surfaces on a table of results. After collecting the results, this should be shown on a set of tables and then placed on a stratified bar graph showing all the sites, the colour of the starfish (on the x- axis) and results of relative fitness(on the y-axis) showing a good visualisation of the experiment. A paired t-test should be done as we want to see the difference between two variables which are the light and dark rocky surfaces for the same sample which is the colour of the starfish through their means. It should then be concluded by seeing which morph has a higher relative fitness and conclude to see if there is an effect. If the p-value is lesser or equal to the significance value, then the hypothesis should be rejected if the p-value is higher than the significance value the hypothesis should be accepted. Figure 2: Purple and orange ochre stars on rocky surfaces Carrying out an experiment in a natural environment is an advantage as this can be reflected on real life therefore having higher ecological validity. However, doing this experiment can have some disadvantages, even though this is cost-effective and done in a natural environment, we do not know how reliable these results will be because the collection of results can have some inaccuracy. Also, it also has to be understood that many other biotic and abiotic factors can affect this experiment. As it is done in the natural environment there will be issues with Pisaster ochraceus being predated by sea otters or even seagulls which can have an effect on results and also making it less generalisable. Air temperature and water temperature can also have an effect on these species as well and it cannot be controlled which can create issues on results. Also, by using a quadrat, it can be prone to human errors (miscounting or overcounting) and having randomly spaced quadrats, can miss out individual species therefore showing under-representative estimates and results in the populations of the Pisaster ochraceus . More repeats would have to be done throughout the years to collect more accurate results and also be tested by other variables such as temperature, wave exposure and even pH of seawater to see if this also affects relative fitness of Pisaster ochraceus with different colouration. It is important to think about the ethical considerations as it is a natural area and these species organisms live there and it should not be damaged before, during and after the experiment. The creatures must be respected as well as the environment they live in. With many equipment being used, it is vital not to interfere with the organisms, create litter or disturb the habitat as it will be unethical. In conclusion, this experiment is effective as it is done in a natural environment at different sites but it will be time consuming due to changes in weather and working out the abundance over all the sites for a long period of time. By doing the paired t-test, a difference in the two means can be seen and create smaller effects on error from the samples. Written by Jeevana Thavarajah Related articles: An experiment on castor oil / on pendulums REFERENCES The Biological Bulletin. 2022. Color Polymorphism and Genetic Structure in the Sea Star Pisaster ochraceus | The Biological Bulletin: Vol 211, No 3. [online] Available at: [Accessed 18 January 2022]. Animal Diversity Web. 2022. Pisaster ochraceus. [online] Available at: [Accessed 18 January 2022]. Sanctuarysimon.org. 2022. SIMoN :: Species Database. [online] Available at: [Accessed 18 January 2022]. Rgs.org. 2022. Royal Geographical Society - Fieldwork in schools. [online] Available at: [Accessed 18 January 2022].

Powering life and causing death Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Dual Role of Mitochondria 11/07/25, 09:57 Last updated: Published: 13/05/24, 13:38 Powering life and causing death Mitochondria as mechanisms of apoptosis Mitochondria are famous for being the “powerhouse of cells” and producing ATP for respiration by being the site for the Krebs cycle, the electron transport chain and the location of electron carriers. However, one thing mitochondria are not known for is mediating programmed cell death, or apoptosis. This is a tightly controlled process within a cell to prevent the growth of cancer cells. One way apoptosis occurs is through the mitochondria initiating protein activation in the cytosol (a part of the cytoplasm). Proteins such as cytochrome c activate caspases by binding to them, causing cell death. Caspases are enzymes that degrade cellular components so they can be removed by phagocytes. Mitochondrial apoptosis is also controlled by the B cell lymphoma 2 (BCL-2) family of proteins. They are split into pro-apoptotic and pro-survival proteins, so the correct balance of these two types of BCL-2 proteins is important in cellular life and death. Regulation and initiation of mitochondrial apoptosis Mitochondrial apoptosis can be regulated by the BCL-2 family of proteins. They can be activated due to things such as transcriptional upregulation or post-translational modification. Transcriptional upregulation is when the production of RNA from a gene is increased. Post-translational modification is when chemical groups (such as acetyl groups and methyl groups) are added to proteins after they have been translated from RNA. This can change the structure and interactions of proteins. After one of these processes, BAX and BAK (some examples of pro-apoptotic BCL-2 proteins) are activated. They form pores in the mitochondrial outer membrane in a process called mitochondrial outer membrane permeabilisation (MOMP). This allows pro-apoptotic proteins to be released into the cytosol, leading to apoptosis. Therapeutic uses of mitochondria Dysregulation of mitochondrial apoptosis can lead to many neurological and infectious diseases, such as neurodegenerative diseases and autoimmune disorders, as well as cancer. Therefore, mitochondria can act as important drug targets, providing therapeutic opportunities. Some peptides and proteins are known as mitochondriotoxins or mitocans, and they are able to trigger apoptosis. Their use has been investigated for cancer treatment. One example of a mitochondriotoxin is melittin, the main component in bee venom. This compound works by incorporating into plasma membranes and interfering with the organisation of the bilayer by forming pores, which stops membrane proteins from functioning. Drugs consisting of melittin have been used as treatments for conditions such as rheumatoid arthritis and multiple sclerosis. It has also been investigated as a potential treatment for cancer, and it induced apoptosis in certain types of leukaemia cells. This resulted in the downregulation of BCL-2 proteins, meaning there was decreased expression and activity.The result of the melittin-induced apoptosis is a preclinical finding, and more research is needed for clinical applications. This shows that mechanisms of mitochondrial apoptosis can be harnessed to create novel therapeutics for diseases such as cancer. It is evident that mitochondria are essential for respiration but also involved in apoptosis. Moreover, mitochondria are regulated by the activation of proteins like BCL-2, BAX and BAK. With further research, scientists can develop more targeted and effective drugs to treat various diseases associated with mitochondria. Written by Naoshin Haque Project Gallery

A type of anaemia Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Iron deficiency anaemia 10/07/25, 10:20 Last updated: Published: 27/06/23, 17:10 A type of anaemia This article is no. 2 of the anaemia series. Next article: anaemia of chronic disease . Previous article: Anaemia . Aetiology Iron deficiency anaemia (IDA) is the most frequent in children due to rapid growth (adolescence) and poor diets (infants), and in peri and post -menopausal women due to rapid growth (pregnancy) and underlying conditions. Anaemia typically presents, in around 50% of cases as headache, lethargy and pallor depending on the severity. Less common side effects include organomegaly and Pica which occurs in patients with zinc and iron deficiency and is defined by the eating of things with little to no nutritional value. Pathophysiology Iron is primarily sourced through diet, as haem (Fe2+) and non-haem iron (Fe3+). Fe2+ is sourced through meat, fish, and other animal-based products, Fe2+ can be absorbed directly through the enterocyte via the haem carrier protein1 (HCP1). Fe3+ is less easily absorbed and is mostly found in plant-based products. Fe3+ must be reduced and transported through the duodenum by the enzyme duodenal cytochrome B (DcytB) and the divalent metal transporter 1 (DMT1), respectively. Diagnosis As with any diagnosis, the first test to run would be a full blood count and this will occur with all the anaemias. In suspected cases of anaemia, the Haemoglobin (Hb) levels would be lower than 130 in males and 120 in females. The mean cell volume (MCV) is a starting point for pinpointing the type of anaemia, for microcytic anaemias you would expect to see an MCV < 80. Iron studies are best for diagnosing anaemias, for IDA you would expect most of the results to be low. A patient with IDA has little to no available iron so the body would halt the mechanism’s for storing iron. As ferratin is directly related to storage, low ferratin can be a lone diagnostic of IDA. Total iron-binding capacity (TIBC) would be expected to be raised, as transferrin transports iron throughout the body, the higher it is the more iron it would be capable of binding to. Elliptocytes (tear drop) are elongated RBC, often described as pencil like in structure and are regularly seen in IDA and other anaemias. Typically, one would see hypochromic RBC as they contain less Hb than normal cells, the Hb is what gives red cells their pigment. It’s not uncommon to see other changes in RBC such as target cells, given their name due to the bullseye appearance. Target cells are frequently seen in cases with blood loss. Summary IDA is the most frequent anaemia affecting patients of all age ranges and usually presents with lethargy and headaches. Dietary iron from animal derivatives are the most efficient source of iron uptake. Diagnosis of IDA is through iron studies, red cell morphological investigations alongside clinical presentation, to rule out other causes. Written by Lauren Kelly Project Gallery

Immunosenescence and related therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Ageing and its association with immune decline Last updated: 24/02/25, 11:28 Published: 20/02/25, 08:00 Immunosenescence and related therapies Introduction Ageing is a profoundly complex and integral part of human life. As pharmaceutical developments have occurred, introducing new medicines and therapies such as biologics and antibiotics within the last 100 years, research has begun to look at malignancy at a more macro scale. To be clear, while it has become easier to combat infectious diseases in recent times, the combating of diseases tied to our genetic composition is far more complicated, whether it be autoimmune diseases or onset conditions such as cases of dementia. Ageing is one such case of a process that is hard to combat because the mechanisms that cause it are diverse and currently not fully understood. Strides have been made under a concept known as senescence, which continues to enlighten researchers and the anti-ageing pharmaceutical industry. This article provides a short summary of what immunosenescence is and how we can utilise our understanding to develop therapies for human immunity. What is immunosenescence? Immunosenescence is the change from a healthy, active immune cell phenotype to one that is no longer conventionally active and begins to secrete inflammatory chemical messengers known as the senescence-associated secretory phenotype (SASP) ( Figure 1 ). A most important aspect of senescence is that a cell undergoes cell cycle arrest, meaning it cannot proliferate. You may now question why cells are programmed to senesce if the outcomes are detrimental to the host? It prevents the continued proliferation of old or damaged cells, including cells with uncontrolled proliferation (such as cancer cells). If we stop senescence altogether, we run the risk of accumulating damaged and/or mutated cells, increasing the chances of disease progression, such as through fibrosis and tumorigenesis, so specific targeting and dosage of drug interventions have to be considered. The immune system in particular, displays biological changes that are indicative of senescent progression. These include thymic involution (shrinking of the thymus associated with a decrease in T cell production), inflammaging (chronic inflammation associated with SASP), an increase in mitochondrial stress through metabolic changes, and an increase in differentiated memory T cells (EMRA T cells). Knowledge of these changes can give insight into potential mechanisms to target for therapeutics. Current and developing therapies for immunosenescence Given our expanding understanding of senescence, as of the time of writing, there are no clinically approved drugs for senescence specifically. The development of therapies for diseases such as cancer, heart disease and diabetes (diabetic patients tend to exhibit increased levels of cellular senescence owing to “accelerated ageing”) have been implicated with suppressing senescence. These drugs would be mTOR inhibitors such as Rapamycin, statins, P13K inhibitors, as well as immune checkpoint inhibitors for T cells, such as anti CTLA-4 PD-L1 and PD-L2, and the anti-diabetic metformin, which have all shown in vitro to be effective against high levels of senescent cells. There was also the development of the recent first senolytic drugs dasatinib and quercetin in 2015 that kill senescent cells selectively against non-senescent cells and stand to provide a proof of concept for targeting disease through senescent mechanisms. Conclusion The field of senescence is certainly one to keep an eye on, with a bibliometric analysis in 2023 showing an increase every year in the number of published papers ( Figure 2 ). It may be sooner rather than later that we see this become a trending topic of discussion for treating an array of disease states. Continuous research into specific immune cell subtypes (B, T and NK cells) and their relation to a decline in immunity in response to age can tell us more about potential therapeutic pathways or lifestyle choices that can improve the health of the immunocompromised elderly. One such example of this is Treg-mediated increased glucose consumption in the tumour microenvironment leading to an increase in cell senescence in effector T cells, suggesting that high sugar diets can accelerate tumorigenesis. Our understanding of ageing through senescence will help reduce the mortality rates of elderly groups in decades to come through knowing that mechanisms such as the SASP and altered immune cell function, which can promote disease states. Written by Yaseen Ahmad Related articles: Genetics of ageing and longevity / Accelerated ageing REFERENCES Henson, S.M. and Aksentijevic, D. (2021) ‘Senescence and type 2 diabetic cardiomyopathy: How young can you die of old age?’, Frontiers in Pharmacology , 12. doi:10.3389/fphar.2021.716517. Wang, R. et al. (2017) ‘Rapamycin inhibits the secretory phenotype of senescent cells by a NRF2-independent mechanism’, Aging Cell , 16(3), pp. 564–574. doi:10.1111/acel.12587. Henson, S.M. et al. (2012) ‘Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade’, Immunology , 135(4), pp. 355–363. doi:10.1111/j.1365-2567.2011.03550.x. Islam, M.T. et al. (2023) ‘Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age’, Aging Cell , 22(2). doi:10.1111/acel.13767. Li, C., Liu, Z. and Shi, R. (2023) ‘A comprehensive overview of cellular senescence from 1990 to 2021: A machine learning-based bibliometric analysis’, Frontiers in Medicine , 10. doi:10.3389/fmed.2023.1072359. Herranz, N. and Gil, J. (2018) ‘Mechanisms and functions of cellular senescence’, Journal of Clinical Investigation , 128(4), pp. 1238–1246. doi:10.1172/jci95148. Li, L. et al. (2019) ‘TLR8-mediated metabolic control of human Treg function: A mechanistic target for cancer immunotherapy’, Cell Metabolism , 29(1). doi:10.1016/j.cmet.2018.09.020. Project Gallery

The mechanisms of the disease Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Alzheimer's disease 09/07/25, 10:46 Last updated: Published: 21/07/23, 09:36 The mechanisms of the disease Introduction to Alzheimer’s disease Alzheimer’s disease is a neurodegenerative disease that results in cognitive decline and dementia with increasing age, environmental and genetic factors contributing to its onset. Scientists believe this is the result of protein biomarkers that build-up in the brain and accumulate within neurones. As of 2020, 55 million people suffer with dementia, with Alzheimer’s being a leading cause. Thus, it is crucial we develop efficacious treatments, with final adverse effects. A new drug called Iecanemab, may be the key to a new era of Alzheimer’s treatment… The disease is most common in people over 65, with 1/14 affected in the UK, thus, there is a huge emphasis on defining the disorder and developing drug treatments. The condition results in difficulty with memory, planning, decision making and can result in co-morbidities such as depression or personality change. This short article will explain the pathology of the disorder and the genetic predispositions for its onset. It will also explore future avenues for treatment, such as the drug I ecanemab that may provide, “a new era for Alzheimer’s disease”. Pathology and molecular aspects The neurodegeneration seen in Alzheimer’s has, as far, been associated protein dispositions in the brain, such as the amyloid precursor protein (APP) and Tau tangles. This has been deduced by PET scans and post-mortem study. APP, located on chromosome 21, is responsible for synapse formation and signalling. It is cleaved to b-amyloid peptides by enzymes called secretases, but overexpression of both these factors can be neurotoxic (figure 1). The result is accumulation of protein aggregates called beta-amyloid plaques in neurons, impairing their survival. This deposition starts in the temporo-basal and front-medial areas of the brain and spreads to the neocortex and sensory-motor cortex. Thus, many pathways are affected, resulting in the characteristic cognitive decline. Tau proteins support nerve cells structurally and can be phosphorylated at various regions, changing the interactions they have with surrounding cellular components. Hyperphosphorylation of these proteins result in the Tau pathology in the form of tau oligomer (short peptides) that is toxic to neurons. These enter the limbic regions and neocortex. It is not clearly defined which protein aggregate proceeds the other, however, the amyloid cascade hypothesis suggests that b-amyloid plaque pathology comes first. It is speculated that b-amyloid accumulation leads to activation of the brain’s immune response, the microglial cells, which then promotes the hyperphosphorylation of Tau. Sometimes, there is a large release of pro-inflammatory cytokines, known as a cytokine storm, that promotes neuroinflammation. This is common amongst older individuals, due to a “worn-out” immune system, which may in part explain Alzheimer’s disease. Genetic component to Alzheimer’s disease There is strong evidence obtained through whole genome-sequencing studies (WGS), that suggests there is a genetic element to the disease. One gene is the Apoliprotein E (APOE) gene, responsible for b-amyloid clearance/metabolism. Some alleles of this gene show association with faulty clearance, leading to the characteristic b-amyloid build-up. In the body, proteins are made consistently depending on need, a dysregulation of the recycling process can be catastrophic for the cells involved. PSEN1 gene that codes for the presenilin 1 protein, part of a secretase enzyme complex. As mentioned, the secretase enzyme is responsible for the cleavage of APP, the precursor for b-amyloid. Variants of this gene have been associated with early onset Alzheimer’s disease, due to APP processing being altered to produce a longer form of the b-amyloid plaque. The genetic aspects to Alzheimer’s disease are not limited to these genes, and in actuality, one gene can have an assortment of mutation that results in a faulty protein. Understanding the genetic aspects, may provide avenue for gene therapy in the future. Treatment Understanding the point in which the “system goes wrong” is crucial for directing treatment. For example, we may use secretase inhibitors to reduce the rate of plaque formation. An example of this is the g- secretase BACE1 inhibitor. There is a need for this drug-type to be more selective to its target, as has been found to produce unwanted adverse effects. A more selective approach may be to target the patient’s immune system with the use of monoclonal antibodies (mAb). This means designing an antibody that recognises a specific component, such as the b-amyloid plaque, so it may bind and then encourage immune cells to target the plaque (figure 3). An example is Aducanumab mAb, which targets b-amyloid as fibrils and oligomers. The Emerge study demonstrated a decrease in amyloid by the end of the 78-week study. As of June 2021, Aducanumab received approval from the FDA for prescription of this drug, but this is controversial as there are claims it brings no clinical benefit to the patient. The future of Alzheimer’s disease Of note, drug development and approval is a slow process, and there must be a funding source in order to carry out plans. Thus, particularly in Alzheimer’s, it is relevant to educate the public and funding bodies to supply the financial support to the process. However, with many hits (potential drug candidates), these often fail at phase III clinical trials. Despite this, another mAb, lecanemab, has recently been approved by the FDA (2023), due to its ability to slow cognitive decline by 27% in early Alzheimer’s disease. The Clarity AD study on Iecanemab, found the drug benefited memory and thinking, but also allowed for better performance of daily tasks. This drug is currently being prescribed on a double-blind basis, meaning a patient may either receive the drug or the placebo. This study shows a hope for those suffering from the disease. Drugs that have targeted the Tau tangles, have as far, not been successful in clinical trials. However, the future of Alzheimer’s treatment may be in the combination therapy directed to both Tau protein and b-amyloid. Washington universities neurology department have launched a trial known as Tau NextGen, in which participants will receive both Iecanemab and tau-reducing antibody. Conclusion This article provides a summary to what we know about Alzheimer’s disease and the potential treatments of the future. Overall, the future of Alzheimer’s treatment lies in the combination therapy to target known biomarkers of the disease. Written by Holly Kitley Related articles: CRISPR-Cas9 as Alzheimer's treatment / Hallmarks of Alzheimer's / Sleep and memory loss Project Gallery

It’s been found that the species Dicrurus adsimilis (fork-tailed drongos) uses deception by flexible alarm mimicry to target and carry out food-theft attempts. The deceptive tactics of the fork-tailed drongo were studied which includes the use of false alarm calls and mimicked calls. Research was done on 64 wild drongos in the Kalahari Desert and it was found that the drongos spent more than a quarter of their time watching their target species which included southern pied babblers and meerkats Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Deception by flexible alarm mimicry in an African bird Last updated: 05/11/24 Published: 28/12/22 It’s been found that the species Dicrurus adsimilis (fork-tailed drongos) uses deception by flexible alarm mimicry to target and carry out food-theft attempts. The deceptive tactics of the fork-tailed drongo were studied which includes the use of false alarm calls and mimicked calls. Research was done on 64 wild drongos in the Kalahari Desert and it was found that the drongos spent more than a quarter of their time watching their target species which included southern pied babblers and meerkats. The other species’ would listen to the alarm calls made by drongos and would rush to take cover as they would if it was an alarm call from their species. These alarm calls were beneficial to them as it increased the number of returns from foraging and reduced their vigilance. However, the drongos used this to their advantage and if the target species was to find a large item of food the drongos could produce a false alarm call to make the target species run to cover out of fear which allowed the observing drongo to steal the deserted food. In 42% of cases of false alarms the drongos used a mimicked cry and in another 27% it was a mixture of mimicked and drongo-specific. This could be because target species are more likely to respond to a mimicked alarm call. In the case of babblers, if they heard a mimicked alarm call they would take longer to carry on foraging than with a drongo-specific call. The results show that false alarm calls by drongos work to distract their target but the call should also be frequently changed and not overused for best results. Written by Areebah Khan Related article: Conserving the Californian condor SUMMARISED FROM Flower, T.P., Gribble, M. and Ridley, A.R. (2014) “Deception by flexible alarm mimicry in an African bird,” Science, 344(6183), pp. 513–516.

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

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

How can patients with metastasised cancer be treated? Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Cancer on the Move 09/07/25, 13:31 Last updated: Published: 30/01/24, 19:57 How can patients with metastasised cancer be treated? Introducing and Defining Metastasis Around 90% of patients with cancer die due to their cancer spreading (metastasis). Despite its prevalence, many critical questions remain in the field of cancer research about how and why cancers metastasise. The metastatic cascade has three main steps: dissemination, dormancy, and colonisation. Most cells that disseminate die once they leave the primary tumour, thus, posing an evolutionary bottleneck. However, the few that survive will face another challenge of entering a foreign microenvironment. Those circulating tumour cells (CTCs) acquire a set of functional abilities through genetic alterations, enabling them to survive the hostile environment. CTCs can travel as single cells or as clusters. If they travel in clusters, CTCs can be coated with platelets, neutrophils, and other tumour-associated cells, protecting CTCs from immune surveillance. As these CTCs travel further, they are named disseminated tumour cells (DTCs). These cells are undetectable by clinical imaging and can enter a state of dormancy. The metastatic cascade represents ongoing cellular reprogramming and clonal selection of cancer cells that can withstand the hostile external environment. How does metastasis occur, and what properties allow these cancer cells to survive? How & Why Does Cancer Metastasise? The Epithelial-to-Mesenchymal Transition (EMT) is a theory that explains how cancer cells can metastasise. In this theory, tumour cells lose their epithelial cell-to-cell adhesion and gain mesenchymal migratory markers. Tumour cells that express a mixture of epithelial and mesenchymal properties were found to be the most effective in dissemination and colonisation to the secondary site. It is important to note that evidence for the EMT has been acquired predominantly in vitro , where additional in vivo research is necessary to confirm this phenomenon. Nevertheless, although EMT does not accurately address why cancers metastasise, it provides a framework for how a cancer cell develops the properties to metastasise. Many factors contribute to why cancers metastasise. For example, a lack of blood supply, which occurs when a cancer grows too large, causes the cells in the centre to lack access to the oxygen carried by red blood cells. Thus, to evade cell death, cancer cells detach from the primary tumour to regain access to oxygen and nutrients. In addition, cancer cells exhibit a high rate of glycolysis to supply sufficient energy for its uncontrollable proliferation. However, this generates lactic acid as a by-product, resulting in a low pH environment. This acidic pH environment stimulates cancer invasion and metastasis as cancer cells move away from this hostile environment to evade cell death once again, an effect referred to as the ‘Warburg Effect’. In Figure 2, you can see that multiple interplaying factors that contribute to metastasis. So, how can patients with metastasised cancer be treated? Current Treatments and Biggest Challenges? Depending on what stage the patient presents at and what cancer type, the treatment options differ. Figure 3 shows an example of these treatment plans. For early stages I and II, chemotherapy and targeted treatments are offered, and in specific cases, local surgery is done. These therapies are done to slow the growth of the cancer or lessen the side effects of treatments. An example of treating metastasised prostate cancer includes hormone therapy, as the cancer relies on the hormone testosterone to grow. Currently, cytotoxic chemotherapy remains the backbone of metastatic therapy. However, there are emerging immunotherapeutic treatments under trial. These aim to boost the ability of the immune system to detect and kill cancer cells. Hopefully, these new therapies may improve the prognosis of metastatic cancers when used in complement with conventional therapies, shining a new light into the therapeutic landscape of advanced cancers. Future Directions Recent developments have opened new avenues to discovering potential treatment targets for metastatic cancer. The first is to target the dormancy of DTCs, where the role of the immune system plays an important part. Neoadjuvant ICI (immune checkpoint inhibitor) studies are anticipated to provide insight into novel biomarkers and can eliminate micro-metastatic cancer cells. Also, using novel technology such as single-cell RNA sequencing reveals complex information about the plasticity of metastatic cancer cells, allowing researchers to understand how cancer cells adapt in stressful conditions. Finally, in vivo models, such as patient-derived models, could provide crucial insight into future treatments as they reproduce the patients’ reactions to different drug treatments. There are many limitations and challenges to the research and treatment of cancer metastasis. It is clear, however, that with more studies into the properties of metastatic cancers and the different avenues of novel targets and therapeutics, there is a promising outcome in the field of cancer research. Written by Saharla Wasame Related articles: Immune signals and metastasis / Cancer magnets for tumour metastasis / Brain metastasis / Novel neuroblastoma driver for therapeutics REFERENCES Fares, J., Fares, M.Y., Khachfe, H.H., Salhab, H.A. and Fares, Y. (2020). Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy , 5(1). doi: https://doi.org/10.1038/s41392-020-0134-x . Ganesh, K. and Massagué, J. (2021). Targeting metastatic cancer. 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