A leap forward in primate research Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Monkey see, monkey clone 26/04/26, 15:26 Last updated: Published: 07/09/24, 20:20 A leap forward in primate research Chinese scientists have recently unlocked the secrets of cloning Rhesus monkeys offering new hope for medical breakthroughs. Introduction When we think of cloning, perhaps the first thing that comes to mind is Dolly the sheep, the first mammal ever cloned from an adult cell back in 1996. This groundbreaking achievement inspired a revolution leading to the successful cloning of other mammals such as cattles and pigs. However, cloning primates, especially Rhesus monkeys, has proven to be a significant challenge due to the low success rates and high embryonic losses during development. What is cloning? Cloning is the process of creating an identical genetic copy of an organism. In mammals, this is typically done through a technique called somatic cell nuclear transfer (SCNT). In SCNT, the nucleus (the compartment storing genetic material) from a cell of the animal to be cloned is transferred into an egg cell that has had its own nucleus removed. This hybrid egg cell then develops into an embryo which is implanted into a surrogate mother to grow into a new individual. Despite the success in cloning other mammals, cloning primates has proven to be a significant challenge. However, the potential benefits of cloning primates for medical research make it a worthwhile endeavour. The importance of cloning primates You might be wondering why being able to clone primates is so important. Well, primates like the Rhesus monkey are invaluable models for studying human diseases and create new therapies! The reason we can use them as disease models is because they share about 93% genetic identity and have very similar physiological characteristics with humans. For instance, Rhesus monkeys also experience a decline in their cognitive abilities as they age, and they lose important connections between brain cells in the part of the brain responsible for complex thinking, even when there's no severe brain damage. Moreover, Rhesus monkeys also develop the same kinds of brain changes that we see in people with Alzheimer's disease, such as the buildup of sticky proteins called amyloid-beta and tangled fibres of another protein called tau.These similarities make them excellent models for understanding how human diseases progress and for developing new treatments. So, by cloning these animals, researchers might be able to create monkeys with specific genetic changes that mimic human diseases even more closely. This could allow scientists to study these diseases in greater detail and develop more effective therapies. Cloning primates could give us a powerful tool to fight against some of the most challenging disorders that affect the human brain! A breakthrough in primate cloning Now, a group of scientists in China have made a breakthrough in primate cloning. They successfully cloned a Rhesus monkey using a novel technique called trophoblast replacement (TR). This innovative approach not only helps us better understand the complex process of cloning but also offers a promising way to improve the efficiency of primate cloning, bringing us one step closer to unlocking the full potential of this technology for medical research and beyond. The awry DNA methylation of cloned conkey embryos To understand why cloning monkeys is so challenging, Liao and colleagues (2024) took a closer look at the genetic material of embryos created in two different ways. They compared embryos made through a standard fertility treatment called intracytoplasmic sperm injection (ICSI) with those created via the cloning technique, SCNT. What they found was quite surprising! To make matters worse, the scientists also noticed that certain genes, known as imprinted genes, were not functioning properly in the SCNT embryos. Imprinted genes are a special group of genes that play a crucial role in embryo development. In a healthy embryo, only one copy of an imprinted gene (either from the mother or the father) is active, while the other copy is silenced. But in the cloned embryos, both copies were often incorrectly switched on or off. Here's the really concerning part: these genetic abnormalities were not just present in the early embryos but also in the placentas of the surrogate monkey mothers carrying the cloned offspring. This suggests that the issues arising from the cloning process start very early in development and continue to affect the pregnancy. Liao and colleagues suspect that the abnormal DNA methylation patterns might be responsible for the imprinted gene malfunction. It's like a game of genetic dominos – when one piece falls out of place, it can cause a whole cascade of problems down the line. Piecing together this complex genetic puzzle is crucial for understanding why primate cloning is so difficult and how we can improve its success in the future. By shedding light on the mysterious world of DNA methylation and imprinted genes, Liao and colleagues have brought us one step closer to unravelling the secrets behind monkey cloning. Digging deeper: what does the data reveal? Liao et al. (2024) discovered that nearly half of the cloned monkey foetuses died before day 60 of the gestation period, indicating developmental defects in the SCNT embryos during implantation. They also found that the DNA methylation level in SCNT blastocysts was 25% lower compared to those created through ICSI (30.0% vs. 39.6%). Furthermore, out of the 115 human imprinting genes they examined in both the embryos and placentas, four genes - THAP3, DNMT1, SIAH1, and RHOBTB3 - showed abnormal expression and loss of DNA methylation in SCNT embryos. These findings highlight the complex nature of the reprogramming process in SCNT and the importance of imprinted genes in embryonic development. By understanding these intricacies, scientists can develop targeted strategies to improve the efficiency of primate cloning. The power of trophoblast replacement To avoid the anomalies in SCNT placentas, the researchers developed a new method called TR. In this method, they transferred the inner cell mass (the part of the early embryo that develops into the baby) from an SCNT embryo into the hollow cavity of a normal embryo created through fertilisation, after removing its own inner cell mass. The idea behind this technique is to replace the abnormal placental cells in the SCNT embryo with healthy ones from the normal embryo. And it worked! Using this method, along with some additional treatments, Liao et al. (2024) successfully cloned a healthy male Rhesus monkey that has survived for over two years (FYI his name is Retro!). The ethics of cloning While the scientific advances in primate cloning are exciting, they also raise important ethical questions. Some people worry about the potential misuse of this technology, for instance to clone humans, which is widely considered unethical. Others are concerned about the well-being of cloned animals, as the cloning process can sometimes lead to health problems. As scientists continue to make progress in cloning technology, it is essential to have open discussions about the ethical implications of their work. Rules and guidelines must be put in place to ensure that this technology is developed and used responsibly, with the utmost care for animal welfare and the concerns of society. Looking to the future The successful cloning of a rhesus monkey using TR opens up new avenues for primate research. This technology can help scientists create genetically identical monkeys to study a wide range of human diseases, from neurodegenerative disorders like Alzheimer's and Parkinson's to infectious diseases like HIV and COVID-19. The trophoblast replacement technique developed by Liao et al. (2024) increases the likelihood of successful cloning by replacing the abnormal placental cells in the SCNT embryo with healthy ones from a normal embryo. However, it is important to note that this technique does not affect the genetic similarity between the clone and the original monkey, as the inner cell mass, which gives rise to the foetus, is still derived from the SCNT embryo. Moreover, this research provides valuable insights into the mechanisms of embryonic development and the role of imprinted genes in this process. By understanding these fundamental biological processes, scientists can not only improve the efficiency of cloning but also develop new strategies for regenerative medicine and tissue engineering. As we look to the future, cloning monkeys could help us make groundbreaking discoveries in medical research and develop new treatments for human diseases. However, we must also carefully consider the ethical implications of cloning primates and ensure that this powerful tool is used responsibly and for the benefit of society. Written by Irha Khalid Related articles: Do other animals get periods? / Germline gene therapy (GGT) REFERENCES Beckman, D. and Morrison, J.H. (2021). Towards developing a rhesus monkey model of early Alzheimer’s disease focusing on women’s health. American Journal of Primatology , [online] 83(11). doi: https://doi.org/10.1002/ajp.23289 . Liao, Z., Zhang, J., Sun, S., Li, Y., Xu, Y., Li, C., Cao, J., Nie, Y., Niu, Z., Liu, J., Lu, F., Liu, Z. and Sun, Q. (2024). Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer. Nature Communications , [online] 15(1), p.5. doi: https://doi.org/10.1038/s41467-023-43985-7 . Morrison, J.H. and Baxter, M.G. (2012). The ageing cortical synapse: hallmarks and implications for cognitive decline. Nature Reviews Neuroscience , [online] 13(4), pp.240–250. doi: https://doi.org/10.1038/nrn3200 . Paspalas, C.D., Carlyle, B.C., Leslie, S., Preuss, T.M., Crimins, J.L., Huttner, A.J., Dyck, C.H., Rosene, D.L., Nairn, A.C. and Arnsten, A.F.T. (2017). The aged rhesus macaque manifests Braak stage III/IV Alzheimer’s‐like pathology. Alzheimer’s & Dementia , [online] 14(5), pp.680–691. doi: https://doi.org/10.1016/j.jalz.2017.11.005 . Shi, L., Luo, X., Jiang, J., Chen, Y., Liu, C., Hu, T., Li, M., Lin, Q., Li, Y., Huang, J., Wang, H., Niu, Y., Shi, Y., Styner, M., Wang, J., Lu, Y., Sun, X., Yu, H., Ji, W. and Su, B. (2019). Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development. National Science Review , [online] 6(3), pp.480–493. doi: https://doi.org/10.1093/nsr/nwz043 . Project Gallery

Pathology and emerging therapeutics Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Bone cancer 25/03/26, 16:48 Last updated: Published: 12/10/23, 11:38 Pathology and emerging therapeutics Introduction: what is bone cancer? Primary bone cancer can originate in any b one. However, most cases develop in the long bones of the legs or upper arms. Each year, more than 500 new cases are diagnosed in the United Kingdom (with a projected downward trend). Primary bone cancer is distinct from secondary bone cancer, which occurs when cancer spreads to the bones from another region of the body. The focus of this article is on primary bone cancer. There are several types of bone cancer: osteosarcoma, Ewing sarcoma, and chondrosarcoma. Osteosarcoma originates in the osteoblasts that form bone. It is most common in children and teens, with the majority of cases occurring between the ages of 10 and 30. Ewing (pronounced as YOO-ing) sarcoma develops in bones or the soft tissues around the bones. Like osteosarcoma, this cancer type is more common in children and teenagers. Chondrosarcoma occurs in the chondrocytes that form the cartilage. Chondrosarcoma is most common in adults between the ages of 30 and 70 and is rare in the under-21 age group. Causes of bone cancer include genetic factors such as inherited mutations and syndromes, and environmental factors such as previous radiation exposure. Treatment will often depend on the type of bone cancer, as the specific pathogenesis of each case is unknown. What is the standard treatment for bone cancer? Most patients are treated with a combination of surgical excision, chemotherapy, and radiation therapy. Surgical excision is employed to remove the cancerous bone. Typically, it is possible to repair or replace the bone, although amputation is sometimes required. Chemotherapy involves using powerful chemicals to kill rapidly growing cells in the body. It is widely used for osteosarcoma and Ewing sarcoma but less commonly used for chondrosarcomas. Radiation therapy (also termed radiotherapy) uses high doses of radiation to damage the DNA of cancer cells, leading to the killing of cancer cells or slowed growth. Six out of every ten individuals with bone cancer will survive for at least five years after their diagnosis, and many of these will be completely cured. However, these treatments have limitations in terms of effectiveness and side effects. The limitation of surgical excision is the inability to eradicate microscopic cancer cells around the edges of the tumour. Additionally, the patient must be able to withstand the surgery and anaesthesia. Chemotherapy can harm the bone marrow, which produces new blood cells, leading to low blood cell counts and an increased risk of infection due to a shortage of white blood cells. Moreover, radiation therapy uses high doses of radiation, resulting in the damage of nearby healthy tissues such as nerves and blood vessels. Taken together, this underscores the need for a therapeutic approach that is non-invasive, bone cancer-specific, and with limited side effects. miR-140 and tRF-GlyTCC Dr Darrell Green and colleagues investigated the role of small RNAs (sRNAs) in bone cancer and its progression. Through the analysis of patient chondrosarcoma samples, the researchers identified two sRNA candidates associated with overall patient survival: miR-140 and tRF-GlyTCC. MiR-140 was suggested to inhibit RUNX2, a gene upregulated in high-grade tumours. Simultaneously, tRF-GlyTCC was demonstrated to inhibit RUNX2 expression by displacing YBX1, a multifunctional protein with various roles in cellular processes. Interestingly, the researchers found that tRF-GlyTCC was attenuated during chondrosarcoma progression, indicating its potential involvement in disease advancement. Furthermore, since RUNX2 has been shown to drive bone cancer progression, the identified miR-140 and tRF-GlyTCC present themselves as promising therapeutic targets. CADD522 Dr Darrell Green and colleagues subsequently investigated the impact of a novel therapeutic agent, CADD522, designed to target RUNX2. In vitro experiments have revealed that CADD522 reduced proliferation in chondrosarcoma and osteosarcoma. However, a bimodal effect was observed in Ewing sarcoma, indicating that lower levels of CADD522 promoted sarcoma proliferation, whereas higher levels of the same drug suppressed proliferation. In mouse models treated with CADD522, there was a significant reduction in cancer volumes observed in both osteosarcoma and Ewing sarcoma. Take-home message The results described here contribute to understanding the molecular mechanisms involved in bone cancer. They highlight the anti-proliferative and anti-tumoral effects of CADD522 in treating osteosarcoma and Ewing sarcoma. Further research is necessary to fully elucidate the specific molecular mechanism of CADD522 in bone cancer and to identify potential side effects. Written by Favour Felix-Ilemhenbhio Related articles: Secondary bone cancer / Importance of calcium / Novel neuroblastoma driver for therapeutics Project Gallery

Delving into the impacts of gut bacteria on health Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Gut Microbiome 11/07/25, 10:58 Last updated: Published: 04/04/24, 17:41 Delving into the impacts of gut bacteria on health Inflammatory Bowel Disease The microbiome is hugely important to human health, and has been shown to beneficial to digestion, the immune system and even our mental health when in good working condition. However, disruption to the balance of the microbial flora has likewise been associated with multiple diseases and poor general health. Dysbiosis, or a poor balance, of human microbiome communities has been implicated in a wide range of disease, such as cardiovascular disease, chronic inflammation, obesity and even mental health issues. A diverse and well-balanced microbial community is important for disease prevention, however modern over usage of antibiotics as well as poor diets low in dietary fibre and high in artificial additives can lead to compromised communities dominated by single pathogenic strains of bacteria. The human microbiome plays a critical role in overall health, from providing valuable metabolites to aiding the immune system. Friendly commensal bacteria colonise major regions in our gut, with characteristic diverse communities of microbes inhabiting them. These microbes occupy these niches and outcompete pathogenic organisms, actively preventing infection and disease. In this article we will be specifically looking into the link between the gut microbiome and Inflammatory Bowel disease (IBD), as this is currently one of the most well researched cases of a causal relationship between the microbiome and disease state. Dysbiosis and Disease state Disruption of the gut flora is associated with painful inflammation of the gastrointestinal tract, diagnosed as IBD. Crohn’s disease and Ulcerative Colitis are conditions under the umbrella term of IBD and cause painful swelling and eventually ulcers in the gastrointestinal tract. The exact cause of IBD remains unclear, with the true cause likely a combination of genetics, environmental factors and the gut microbiome. Evidence has come to light that shows a link between disease state and the gut dysbiosis, where they influence each other and are potentially both each other’s cause and effect. Successfully treating IBD has proved difficult; medications focus on alleviating inflammation or other symptoms as antibiotics have shown limited effectiveness in curing the disease. Antibiotics have even been suggested to weaken the immune system long-term, as evidence suggests that antibiotic clearance of commensal bacteria can provide opportunity for pathogenic strains to establish themselves. Medical treatments destabilizing the microbiome can lead to a change in overall metabolism and chronic Clostridium difficile infection. When colonization resistance is compromised there is more opportunity for single bacteria to dominate the community, with antibiotic-associated diarrhoea a common side effect associated with antibiotic induced dysbiosis. Microbial-based therapies Recently potential therapies pivoted to target the microbiota, as reinstating a healthy colony of gut microbials should alleviate the cause of IBD. Previous treatments relied on antibiotics followed by a course of probiotics; however, this has had variable levels of success as the antibiotic treatment can further reduce bacterial diversity in the gut. Probiotics have limited effectiveness in alleviating symptoms; any effect is transient as no probiotic microbial strains are detectable after 2 weeks of stopping intake. In modern clinical trials we have already seen positive results from microbiome treatments in clearing C. difficile infection, such as faecal microbiota transplantation (FMT) therapy. FMT uses faeces from a healthy donor, which are processed and delivered to the gastrointestinal tract of patients. Faeces contain a high microbial load, with up to 1011 bacterium per gram and multiple archaea, fungi and viruses that could not be delivered orally in a probiotic form. Success in resolving dysbiosis through FMT is variable but shows more promise than other therapies. Future Potential Specific forms of IBD such as ulcerative colitis (UC) was first treated with FMT in 1989, with patients reducing medications within a week of enema treatments and remaining clinically disease free for multiple years after treatment. More recent trials have had more variable levels of remission, suggesting donor compatibility, disease prevalence and engraftment of the microbiota all factor into the success of FMT. There is potential in this therapy, as FMT has proved more robust than previous treatments for IBD. Modern research into the relationship between disease and gut flora has come a long way in a relatively short time and shows there is much potential for future research in this area. Written by Charlotte Jones Related articles: the power of probiotics / Crohn's disease / the dopamine connection / Diverticular disease / Nanoparticles on gut health / Microbes in charge Project Gallery

A type of anaemia Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Iron deficiency anaemia 09/05/26, 14:47 Last updated: Published: 27/06/23, 18:10 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 occur 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 TIBC 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 bulls-eye 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

You can have endometriosis and PMOS at the same time Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Are PMOS and endometriosis sisters? 13/06/26, 16:45 Last updated: Published: 30/01/24, 21:33 You can have endometriosis and PMOS at the same time The label of polyendocrine metabolic ovarian syndrome, PMOS (previously known as PCOS) or endometriosis can have physical and emotional consequences for women. It is important for both male and females to gain a better understanding of such conditions, the symptoms and the challenges they pose. Such knowledge can act as physical and emotional support in times of need. It creates a safe space where the person with PMOS is comfortable discussing their experiences, feelings and concerns knowing they are being heard and supported by the right people. With research fast developing there is a plethora of information out there, so WHAT do you believe in and WHAT do you ignore and WHOM do you believe and WHOM do you ignore? Endometriosis and PMOS both affect females and can have similar symptoms. However, the causes and some key symptoms are different. Endometriosis is a painful disorder in which tissue that normally lines the inside of your uterus grows outside the uterus. (Read more on Endometriosis breakthrough ). PMOS is an endocrine system disorder where small fluid-filled sacs develop in the ovaries. You can have endometriosis and PMOS at the same time. A 2015 study found that women with PMOS had a higher risk for a diagnosis of endometriosis. Another 2014 study determined that there is a strong link between endometriosis and PMOS with pelvic pain and trouble getting pregnant. What is a normal menstrual cycle? Let’s polish up the basics! The brain, ovaries and uterus work together to prepare the body per month for pregnancy. Follicle-stimulating Hormone (FSH) and Luteinising Hormone (LH) are made by the pituitary gland and progesterone and oestrogen are made in the ovaries. Many females with PMOS do not ovulate regularly and it may take these females longer to become pregnant. Irregular periods results in months where ovulation does not occur. Where the ovaries do not produce progesterone the lining of the uterus becomes thicker but shedding is very irregular which can lead to heavy and prolonged bleeding. PMOS affects 1 in 10 women in the UK. Women with PMOS experience irregular menstrual cycles, acne, excess hair growth, infertility, pregnancy complications and cardiovascular disease. PMOS can be associated with weight gain and obesity in approximately one-half of females. Females with PMOS can also be at increased risk of other problems that can impact quality of life. These include depression and anxiety, sexual dysfunction and eating disorders. Although PMOS is not ‘completely’ reversible there are many ways you can minimise the symptoms. Most females can lead a normal life and are able to conceive without significant complications. A pelvic examination is requested by your GP to assess the ovaries for a diagnosis to be made. Imaging tests for examining the ovaries are pelvic and intravaginal ultrasonography, however, the latter may be extremely uncomfortable if sexually inactive. Note: As of Oct 2025, NICE has announced it will adapt the International PMOS Guideline for the UK. Please be aware this article acts to capture your attention, encouraging you to delve further into the subject and continue your self-education on this topic and by no means is everything about PMOS. It is essential to consult with a healthcare professional if you suspect you may have symptoms of either PMOS or endometriosis. Proper diagnosis and management can help address specific concerns and improve overall reproductive health. Written by Khushleen Kaur Related articles: Endometriosis breakthrough / Underreporting in endometriosis / Gynaecology REFERENCES R. Hart and D. A. Doherty, Fertility Specialists of Western Australia (R.H.), Bethesda Hospital, 6008. K. J. Holoch, R. F. Savaris, D. A. Forstein, P. B. Miller, H. Lee Higdon, C. E. Likes and B. A. Lessey, https://doi.org/10.5301/je.5000181 , 2014, 6, 79–83. R. J. Norman, D. Dewailly, R. S. Legro and T. E. Hickey, The Lancet, 2007, 370, 685–697. Project Gallery

Properties of space Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Topology in action 17/02/25, 14:51 Last updated: Published: 29/09/23, 21:09 Properties of space Let’s say I put a sphere in front of you. I’m sure you could go through and tell me the basic facts and formulas surrounding it, many if which containing Pi. And even better, if you were a bit more fluent in maths, you could go further and start telling me about the geometry of the shape, say how the gradient had to disappear at a certain point or an assortment of many other things. But if we dive a little deeper into pure maths, it starts getting a little more complicated. When labels like Hausdorff get casually thrown about (meaning you can always separate two distinct points with an open boundary, which you certainly can do on a sphere!) it can really build up and become quite hard, especially if someone then puts in front of you two spheres stuck together. This is where the study of topology comes in and starts helping out, allowing us to start to categorise certain spaces without having to worry about all the small details that could catch you out. Topology is certainly found in the purer side of maths, generally seen as one of the more abstract modules to be taking at undergraduate level (as seen by the exam scores). But thinking of it just as some far away concept disconnected with the rest of the world would be foolish. Thinking back to what I said before about gradient fields on a sphere, this is more commonly known in maths as the “Hairy Ball Theorem” named as such as if you had a ball of hair, you wouldn’t be able to smooth it all out without a cow’s lick. And in mathematical terms it means that a continuous vector field has to disappear at a certain point. And maybe not readily apparent but this comes up in loads of places, the most obvious of which is that two points on the Earth will always have the exact temperature! But moving to Biology we see a lot more applications, even as early as in A-level study. Just thinking about how a protein will fold is all to do with the topological properties of them. DNA is a bit more complex understandably, with more base pairs it becomes incredibly flexible, able to bend into many shapes, but like topological spaces this flexible has limits. It doesn’t pass through itself nor tear, so it allows us to start applying our theorems to it. A key one of these is Knot theory, which of course is the study of knots. Knots in maths are defined as having no open ends and being complex, which helpfully is exactly like DNA! As you hopefully know, its coiled form has no open ends, and in order to untangle it we have to go through the process of cutting at double points. The amount of times this is needed to untangle is called the 'unknotting number' in topology and this mathematical modelling of the process allows biologists to move away from the microscope and still get a more accurate look on what’s happening. Written by Tom Murphy Related article: Quantum chemistry 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, 11:54 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

'Manis pentadactyla' is the dominant pangolin species in China Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Pangolins: from poached to protected Last updated: 27/03/25, 11:15 Published: 27/02/25, 08:00 'Manis pentadactyla' is the dominant pangolin species in China This is article no. 4 in a series on animal conservation. Next article: How Gorongosa National Park went from conflict to community . Previous article: Beavers are back in Britain Pangolins are a group of eight scaled mammal species from Asia and Africa. They are being poached mainly for their scales and meat, driving them to dangerously low numbers. Although commercial trade is banned for all species, pangolins are the most illegally trafficked animals in the world. One pangolin species has a fascinating story because of its appeal to traditional medicine and demand in a populated country. That species is the Chinese pangolin Manis pentadactyla , and this article will describe its threats and conservation efforts. About pangolins in China Manis pentadactyla is the dominant pangolin species in China, living south of the Yangtze River ( Figure 1 ). The Sunda pangolin Manis javanica has a tiny habitat in southwest China ( Figure 1 ). Pangolins prefer natural forests, with an ambient temperature of 18-27°C and plenty of termites and ants to eat. Both Chinese species were classified as critically endangered in 2014, though accurately estimating pangolins' distribution and population size is complex. This is because they are nocturnal, solitary, and live underground. Pangolins also make no obvious sounds, or leave no apparent traces, for scientists to detect their presence. Despite these challenges, Chinese scientists are learning more about pangolin habitat to improve conservation strategies. Threats facing Chinese pangolins Chinese pangolins are critically endangered for various human-caused reasons ( Figure 2 ). The biggest reason is poaching because pangolin meat is a local delicacy, and its scales, bones, and blood are used in traditional Chinese medicine. Pangolin scales have recently been removed from the official list of ingredients for Chinese medicine, but that has not stopped hospitals from selling them. In a recent study, only a third of Chinese hospitals selling roasted pangolin scales had the required permit. Permits are also needed to sell or manufacture patented medicines containing pangolin scales, considered the gold standard for treating many conditions. Because these medicines and pangolin meat are so revered, one hunted pangolin sells for up to 90,000 yuan (≈£9800). This has incentivised the hunting and illegal trafficking of non-native pangolin species into China - where they could outcompete, or spread diseases to native species. Thus, illicit trade for traditional medicine threatens Chinese pangolins. Habitat destruction has made Chinese pangolins more vulnerable to poaching. Natural forests are being destroyed to grow crops, grow economic trees like rubber, or build human infrastructure. Farms or rubber plantations have fewer ants and termites than natural forests, so pangolins cannot survive there. As a result, in some parts of China, the pangolin geographical range halved in 30 years. With acres of this unsuitable habitat separating fragments of forest, pangolins may struggle to find mates, and inbreeding could be an issue. Thus, habitat loss is contributing to the decline of the Chinese pangolin. Conservation Conservation measures were taken in the last few decades in response to the pangolin population decline. In China, hunting pangolins was first restricted in 1987, and they were given legal protection in 1989. The Chinese government tightened this protection in 2020 after suggestions that pangolins were an intermediate species for SARS-CoV-2 to transmit from bats to humans. In addition to national restrictions, international authorities restricted pangolin trade, and the Chinese government ran public awareness campaigns about their endangered status ( Figure 3 ). Pangolins also have 100,000 squared kilometres of protected habitat in China, though this is only 9% of what models predict as a suitable pangolin habitat. Habitat protection and trade restrictions are essential to protect pangolins because captive breeding has either failed or acted as a front for illegal trafficking. Although Chinese pangolin conservation has come far in the last 40 years, more can be done. Conclusion Humans have driven Chinese pangolins to near extinction, mainly by hunting for traditional medicine ingredients and destroying native habitats. Conservation efforts have primarily involved legal and habitat protection, but pangolins are challenging to monitor and impossible to breed in captivity. Hopefully, public awareness and a clampdown on illegal trafficking will help to save this unique mammal species. Written by Simran Patel Related articles: Conservation of marine iguanas / Galapagos tortoises REFERENCES Challender, D. et al. (2013) IUCN Red List of Threatened Species: Manis pentadactyla . IUCN Red List of Threatened Species . Available from: https://www.iucnredlist.org/en (Accessed 23rd October 2024). Convention On International Trade In Endangered Species Of Wild Fauna And Flora (2017) Appendices I, II and III valid from 4 October 2017 . Available from: https://cites.org/sites/default/files/eng/app/2017/E-Appendices-2017-10-04.pdf . Mammoser, G. (20th February 2017) Chinese Police Go After ‘Pangolin Princess’ Who Proudly Eats Endangered Species. VICE . Available from: https://www.vice.com/en/article/chinese-police-go-after-pangolin-princess-who-proudly-eats-endangered-species/ (Accessed 23rd October 2024). Wang, Y., Turvey, S.T. & Leader-Williams, N. (2023) The scale of the problem: understanding the demand for medicinal pangolin products in China. Nature Conservation . 52: 47–61. Available from: https://doi.org/10.3897/natureconservation.52.95916 (Accessed 23rd October 2024). Xinhua News Agency (2015) Opinions of the Central Committee of the Communist Party of China and the State Council on Accelerating the Construction of Ecological Civilization . Beijing: The Central Government of the People’s Republic of China. Available from: https://www.gov.cn/xinwen/2015-05/05/content_2857363.htm (Accessed 23rd October 2024). Zhang, F., Chen, Y., Tang, X., Xi, F., Cen, P., Pan, Z., Ye, W. & Wu, S. (2024) Predicting the distribution and characteristics of Chinese pangolin habitat in China: Implications for conservation. Global Ecology and Conservation . 51: e02907. Available from: https://www.sciencedirect.com/science/article/pii/S2351989424001112 (Accessed 23rd October 2024). Zhang, F., Wang, W., Mahmood, A., Wu, S., Li, J. & Xu, N. (2021) Observations of Chinese pangolins ( Manis pentadactyla ) in mainland China. Global Ecology and Conservation . 26: e01460. Available from: https://www.sciencedirect.com/science/article/pii/S235198942100010X (Accessed 23rd October 2024). Zhang, F., Wu, S. & Cen, P. (2022) The past, present and future of the pangolin in Mainland China. Global Ecology and Conservation . 33: e01995. Available from: https://www.sciencedirect.com/science/article/pii/S235198942100545X (Accessed 19th October 2024). Project Gallery

NMR is far more elementally diverse and is applicable to any nucleus with a spin quantum number (I) greater than 0 Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The world of inorganic NMR Last updated: 29/05/26, 18:38 Published: 04/06/26, 08:00 NMR is far more elementally diverse and is applicable to any nucleus with a spin quantum number (I) greater than 0 Introduction “It’s an organic chemist’s world, and we are just living in it” is my take on a popular idiom which has never felt more relevant than in the context of NMR spectroscopy. Since our first introductions to nuclear magnetic resonance (NMR), we are often led to believe that the technique is only applicable to proton (¹H) and carbon (¹³C) nuclei. However, NMR is far more elementally diverse and is applicable to any nucleus with a spin quantum number (I) greater than 0. This article will introduce fluorine (¹⁹F) and phosphorus (³¹P) NMR spectroscopy before considering the “satellite spectra” that arise from nuclei that are not 100% naturally abundant. Finally, the article will explore quadrupolar nuclei, proving that NMR extends far beyond the constraints of organic chemistry. Phosphorus and Fluorine Before discussing ¹⁹F and ³¹P NMR spectroscopy, it is worth considering how a ¹H NMR spectrum is used to characterise a molecule. First, the chemical shifts of particular protons depend on their electronic environments, with protons surrounded by more electronegative elements appearing athigher chemical shifts as they interact more strongly with the applied magnetic field. Splitting patterns are determined by the number of neighbouring nuclei and follow the 2nI + 1 rule, where n is the number of neighbouring nuclei and I is the spin quantum number of the coupled nucleus. Peak intensities are predicted by Pascal’s triangle. These rules are applicable to any spin‑½ nuclei, including ³¹P and ¹⁹F. For example, the inorganic anion [PF₆]⁻ is frequently used as a stabilising counterion in many cationic inorganic complexes and can be readily characterised using NMR. Considering the ³¹P NMR spectrum first, the phosphorus nucleus couples to six equivalent ¹⁹F nuclei and therefore produces a septet splitting pattern. Alternatively, in the ¹⁹F NMR spectrum, six equivalent fluorine nuclei couple to one ³¹P nucleus, producing a doublet. Satellite Spectra The term “satellite spectra” arises when considering coupling to spin‑active NMR nuclei that are not 100% naturally abundant. This usually occurs because multiple isotopes of an element exist, but only one is NMR‑active. For example, tungsten has five naturally occurring isotopes, but only one is NMR‑active (¹⁸³W), with a natural abundance of 14.3%. To illustrate how this affects the appearance of an NMR spectrum, consider the compound trans‑[W(PPh₃)₂(CO)₄], where the two triphenylphosphine ligands are chemically equivalent. We would initially expect a singlet in the ³¹P NMR spectrum. However, the ³¹P nuclei can also couple to the tungsten centre. Rather than observing a simple doublet, the spectrum appears as a singlet with a small superimposed doublet. This occurs because 85.7% of the molecules contain an inactive tungsten isotope, while 14.3% contain ¹⁸³W. Quadrupolar Nuclei NMR spectra can also be obtained for nuclei with spin quantum numbers where I ≥ 1, known as quadrupolar nuclei. While less commonly analysed by NMR, quadrupolar nuclei account for over 70% of the NMR‑active nuclei on the periodic table. An example of where quadrupolar NMR spectroscopy is effective is in studying the tetrafluoroaluminate ion, [AlF₄]⁻. The ¹⁹F NMR spectrum of this compound appears as a sextet with equal line intensities, as quadrupolar nuclei still obey the 2nI + 1 rule. The splitting pattern indicates that the ²⁷Al nucleus has a spin quantum number of 5/2, and the peak intensities are no longer governed by Pascal’s triangle. However, quadrupolar nuclei are not commonly studied by NMR because their non‑spherical charge distributions often lead to extensive peak broadening. [AlF₄]⁻ acts as a useful exception, where the peaks resolve because of the symmetry in a tetrahedral geometry. Quadrupolar NMR is therefore most effective in highly symmetric environments, such as octahedral (Oₕ) and tetrahedral (T_d) geometries. Conclusion In conclusion, the elemental diversity of NMR spectroscopy makes it one of the most powerful characterisation techniques available to a synthetic chemist. While this article has focused on inorganic applications of NMR, the scope of the technique is far broader. From using NMR to investigate molecular diffusion to advanced 2D NMR methods including COSY and NOESY, NMR spectroscopy dominates the analytical landscape like few others. Written by Antony Lee Related articles: Advances in mass spectrometry technology Project Gallery

Implementing established physical theories into the constructions of the future Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Building Physics Last updated: 03/04/25, 11:39 Published: 20/02/25, 08:00 Implementing established physical theories into the constructions of the future From the high rise establishments that paint the expansive London skyline to the new build properties nestled within thriving communities, buildings serve as a beacon of societal needs. The planned and precise architecture of buildings provides shelter and comfort for individuals, as well as meet business agendas to promote modern day living. Additionally, buildings serve a purpose as a form of protection where, according to the World Health Organisation (WHO), the design and construction of buildings is to create an environment suitable for human living: more favourable than the state of the natural environment outdoors construction and building protects us from: extremes of temperature moisture excessive noise To sustain these pivotal agendas, a comprehensive analysis of the physical factors within the environment of buildings, including temperature, light and sound are required for design and legislation for a building to function. The field of ‘Building Physics’ primarily addresses these physical factors to innovate ‘multifunctional solutions’, be more efficient, and build upon present designs, which can be adapted for future use. Moreover, the built environment is regarded as one of the biggest carbon emissions on the planet, so using building physics as an early design intervention can reduce energy consumption and minimise carbon emissions. This supports global manifestos of moving towards net zero and decreasing the likelihood of the detrimental effects caused by climate change. The main components of Building Physics Building Physics is composed of examining the functions of an interior physical environment, including air quality, thermal comfort, acoustics comfort (sound), and light : Air quality: Ventilation is needed for maintaining a safe environment and reducing the quantity of stale air - consisting of carbon dioxide and other impurities - within an interior environment. Air infiltration also contributes to a significant heat loss, where it is important to provide intentional ventilation to increase the efficiency of energy transfers within the building. Thus, good ‘airtightness’ of a building fabric, which can be considered as the building’s resistance to unintentional air infiltration or exfiltration, can enable planned airflows for ventilation. Thermal: The biggest influence within the field of Building Physics stems from an understanding of heat conductivity depending on the density and moisture content of the material, as well as heat transfers - conduction, convection, radiation and transition - to determine the suitability of materials used for construction. For example, a material such as a solid wood panel for walls and ceilings is favourable as it can be installed in layers, providing even temperature fields across the surface. It is important that a building has the ability to isolate its environment from external temperature conditions and have the correct building envelope - a barrier that separates the interior and exterior of a building. Acoustics: A regulated control of sound within buildings contributes towards maintaining habitable conditions for building users to make sure that sound is loud, undistorted, and the disturbances are reduced. Acoustics can be controlled and modified through material choices, such as installing sound-absorbing material. These materials can be adapted to reduce sound leakage, which are common in air openings, such as ventilators and doors, that are more likely to transmit sound than adjacent thicker walls. Light: Light provides an outlook of viewing an environment in an attractive manner, particularly using daylight as a primary source of enhancing the exterior of a building, whilst also functioning within a building. One strategy used to fulfil the purpose of light in buildings is designing windows for the distribution of daylight to a space. The window design has a divisive effect on the potential daylight and thermal performance of adjacent spaces, so it needs to be closely checked using the standardised methods, in order to be suitable for use. Additionally, as windows are exposed to the sky, daylighting systems can adapt windows to transmit or reflect daylight as a function of incident angle, for solar sharing, protection from glare and redirection of daylight. Overall, a key objective of sustaining a safe and eco-friendly building is to ensure that the space has proper heat and humidity aligning with a suitable degree of acoustic and visual comfort in order to sustain the health of the people using the building. Particularly within modern society, a combination of Building Physics principles and digitalised software, such as Building Information Modelling (BIM), can enhance the design process of a building to provide healthy environments for generations to come. Written by Shiksha Teeluck Related article: Titan Submersible REFERENCES Unsplash. A construction site with cranes [Internet]. [Accessed 2 January 2025]. Available from: https://unsplash.com/photos/a-construction-site-with-cranes-mOA2DAtcd1w . Katunský D, Zozulák M. Building Physics . 2012. ISBN: 978-80-553-1261-3. Partel. Building Physics [Internet]. [Accessed 2 January 2025]. Available from: https://www.partel.co.uk/resources/building-physics/#:~:text=According%20to%20WHO%20(World%20Health,%3A%20in%20contrast%2C%20allows%20productions . RPS Group. A day in the life of a senior building physics engineer [Internet]. [Accessed 4 January 2025]. Available from: https://www.rpsgroup.com/insights/consulting-uki/a-day-in-the-life-of-a-senior-building-physics-engineer/ . Cyprus International University. What is Building Physics and Building Physics Problems in General Terms [Internet]. [Accessed 6 January 2025]. Available from: /mnt/data/What_Is_Building_Physics_and_Building_Ph.pdf. Centre for Alternative Technology. Airtightness and Ventilation [Internet]. [Accessed 6 January 2025]. Available from: https://cat.org.uk/info-resources/free-information-service/eco-renovation/airtightness-and-ventilation/#:~:text=With%20good%20airtightness%2C%20effective%20ventilation,won't%20work%20as%20intended . KLH. Building Physics [Internet]. [Accessed 6 January 2025]. Available from: https://www.klh.at/wp-content/uploads/2019/10/klh-building-physics-en.pdf . Watson JL. Climate and Building Physics [Internet]. [Accessed 6 January 2025]. Available from: https://calteches.library.caltech.edu/98/1/Watson.pdf . Ruck N, Aschehoug Ø, Aydinli S, Christoffersen J, Edmonds I, Jakobiak R, et al. Daylight in Buildings - A source book on daylighting systems and components . 2000 Jun. Synergy Positioning Systems. How BIM Saves Time & Money for Construction Businesses [Internet]. [Accessed 6 January 2025]. Available from: https://groupsynergy.com/synergy-positioning-news/how-bim-saves-time-money-for-construction-businesses . Project Gallery