Vicuñas are members of the camelid family Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The cost of coats: celebrating 55 years of vicuña conservation 08/03/26, 18:25 Last updated: Published: 09/10/24, 15:03 Vicuñas are members of the camelid family This is article no. 1 in a series on animal conservation. Next article: Conserving the California condor . Is the softest coat in the world worth the near-extinction of a species? Just ask a vicuña, the wild cousin of llamas and alpacas. After being widely hunted in South America in the mid-20th century, the vicuña population thrives. Their recovery is considered one of the earliest successes in modern wildlife conservation, setting a precedent for sustainable development. October 2024 marked the 55th anniversary of the first international agreement to conserve these furry friends. In its honour, here is the story of vicuña conservation. What are vicuñas? Vicuñas have a unique biology. They are members of the camelid family ー which includes llamas, alpacas, and camels. Vicuñas live in high-altitude arid grasslands in South America (Figure 1). Their families consist of one alpha male, multiple females, and their offspring – while bachelor males form their own groups. Unlike other camelids, vicuña families remain together for most of the year. Vicuñas are herbivores with characteristic grazing and defecating behaviours that shape the surrounding plant community. Therefore, their ecological role cannot be underestimated. How vicuñas nearly went extinct However, vicuñas are hunted by humans because their wool is the finest and softest in the world. They are difficult to domesticate, and their habitat has no hiding spots, so they are easy poaching targets. Their intricate social structure means killing one vicuña has unforeseen impacts on the rest of the population. Consequently, expensive wool comes at the expense of a fascinating species. Demand for ultra-fine vicuña wool made hunting the animals a lucrative business in South America. Although 15th-16th century Inca rulers wore high-end clothing made from vicuña wool, it was usually harvested without killing the animals. European colonisation in the 19th-20th centuries opened vicuña wool to a wealthy international market, making poaching more popular and reckless than under Inca rule. These inconsiderate hunting practices continued after South American countries gained independence. As the luxurious wool remained in demand, the vicuña population decreased by over 99% between 1940 and 1965. Conservation policies saved the vicuñas South American national governments soon realised that indiscriminate vicuña hunting had to stop. As well as being ecologically important, vicuñas should not be allowed to go extinct because of their economic value. Peru had the largest proportion of the vicuña population, so in 1966 its government set up a nature reserve called Pampa Galeras. Creating this reserve involved negotiating with rural communities so that both people and vicuñas benefitted, for example, by employing locals at the reserve. This was one of the earliest examples of what is now known as sustainable development, which provides rural communities with a way of life that works alongside ecosystems rather than damaging them. Scientists found that vicuñas changed their social structures inside Pampa Galeras to maximise reproductive success. A 1987 study suggested that because females had more time to graze without the constant threat of predators and poachers, their reproductive success was higher. The creation of this reserve was the first of many successful steps South America took in the 1960s towards vicuña recovery. In October 1969, Argentina, Chile, Ecuador, and Bolivia joined Peru in the efforts to conserve vicuñas. Their Convention for the Conservation of the Vicuña banned international trade and massively restricted hunting. Since the convention successfully led to a rise in vicuña numbers, it was modified in 1979 so that sustainable vicuña wool could be sold. Meanwhile, conservation laws were being established in the United States and European Union, the wildlife trade regulator CITES was established, and public awareness about the biodiversity crisis was rising. This international effort saved vicuñas from extinction, and today there are 350,000 to 500,000 of them ( Figure 2 ). Although governments have played a huge role in conserving the vicuña, local communities have also contributed. People in Chile and Peru have revived the non-lethal, Inca traditional way of shearing vicuña to harvest their wool. This has many benefits: locals are de-colonising their culture and re-connecting with their heritage, the wool provides a source of income, and the vicuña population remains stable. Vicuñas were classified as ‘least concern’ for conservation by the International Union for Conservation of Nature in 2018. Climate change, mite infestations, and competition with livestock are affecting the population today – but to a much smaller extent than poaching was. Thus, vicuñas are back to freely roaming the Andes. Conclusion Conserving the vicuña relied on political willpower and community involvement. In the 55+ years since, ecologists have used this charismatic and distinctive animal to galvanise wildlife conservation worldwide. The vicuña’s story should also remind us that what we wear has financial and ecological costs. Written by Simran Patel Related articles: Conservation of marine igunanas / Gal á gapos tortoises REFERENCES Acebes, P., Wheeler, J., Baldo, J.L., Tuppia, P., Lichtenstein, G., Hoces, D. & Franklin, W.L. (2018) Vicuna: Vicugna vicugna . The IUCN Red List of Threatened Species 2018 . Available from: https://ri.conicet.gov.ar/handle/11336/178499 (Accessed 12th September 2024). Bosch, P.C. & Svendsen, G.E. (1987) Behavior of Male and Female Vicuna (Vicugna vicugna Molina 1782) as It Relates to Reproductive Effort. Journal of Mammalogy . 68 (2): 425–429. Available from: https://doi.org/10.2307/1381491 (Accessed 23rd September 2024). González, B. et al. (2019) Phylogeography and Population Genetics of Vicugna vicugna : Evolution in the Arid Andean High Plateau. Frontiers in Genetics . 10. Available from: https://doi.org/10.3389/fgene.2019.00445 (Accessed 22nd September 2024). Karandikar, H., Donadio, E., Smith, J.A., Bidder, O.R. & Middleton, A.D. (2023) Spatial ecology of the Vicuña ( Lama vicugna ) in a high Andean protected area. Journal of Mammalogy . 104 (3): 509–518. Available from: https://doi.org/10.1093/jmammal/gyad018 (Accessed 11th September 2024). Lyster, S. (1985) VICUNA. In: International Wildlife Law: An Analysis of International Treaties concerned with the Conservation of Wildlife . Cambridge: Cambridge University Press: 88–94. Nolan, D. (2025) How an Ancestral Peruvian Ceremony Is Saving the Once-Endangered Vicuña . Smithsonian Magazine . Available at: https://www.smithsonianmag.com/travel/how-an-ancestral-peruvian-ceremony-is-saving-the-once-endangered-vicuna-180986933/ (Accessed: 7 March 2026). Reider, K.E. & Schmidt, S.K. (2021) Vicuña dung gardens at the edge of the cryosphere. Ecology . 102 (2): 1–3. Available from: https://www.jstor.org/stable/26998110 (Accessed 11th September 2024). UNESCO (2024) Ancestral practice promotes vicuña conservation and sustainable . unesco.org . Available at: https://www.unesco.org/en/articles/ancestral-practice-promotes-vicuna-conservation-and-sustainable-development-chiles-lauca-biosphere (Accessed: 7 March 2026). Vilá, B. & Arzamendia, Y. (2022) Weaving a vicuña shawl. Pastoralism . 12 (1): 46. Available from: https://doi.org/10.1186/s13570-022-00260-6 (Accessed 11th September 2024). Wakild, E. (2020) Saving the Vicuña: The Political, Biophysical, and Cultural History of Wild Animal Conservation in Peru, 1964–2000. The American Historical Review . 125 (1): 54–88. Available from: https://doi.org/10.1093/ahr/rhz939 (Accessed 11th September 2024). Yacobaccio, H. (2009) The Historical Relationship Between People and the Vicuña. In: Gordon, I.J., ed. The Vicuña: The Theory and Practice of Community Based Wildlife Management . Boston, MA: Springer US: 7–20. Project Gallery

Nanoparticles have unique properties Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Nanoparticles: the future of diabetes treatment? 17/07/25, 11:52 Last updated: Published: 06/05/24, 14:20 Nanoparticles have unique properties Diabetes mellitus is a chronic metabolic disorder affecting millions worldwide. Given its myriad challenges, there is a substantial demand for innovative therapeutic strategies in its treatment. The global diabetic population is expected to increase to 439 million by 2030, which will impose a significant burden on healthcare systems. Diabetes occurs when the body cannot produce enough insulin, a hormone crucial for regulating glucose levels in the blood. This deficiency leads to increased glucose levels, causing long-term damage to organs such as the eyes, kidneys, heart, and nervous system, due to defects in insulin function and secretion. Nanoparticles have unique properties making them versatile in their applications and are promising to help revolutionise the future of the treatment of diabetes. This article will explore the potential of this emerging technology in medicine and will address the complexities and issues that arise with the management of diabetes. Nanoparticles have distinct advantages: biocompatibility, bioavailability, targeting efficiency and minimal toxicity, making them ideal for antidiabetic treatment. The drug delivery is targeted, making the delivery precise and efficient, avoiding off-target effects. Modifying nanoparticle surfaces enhances therapeutic efficacy, enabling targeted delivery to specific tissues and cells, while reducing systemic side effects. Another currently researched key benefit is real-time glucose sensing and monitoring, which addresses a critical aspect in managing diabetes, as nanoparticle-based glucose sensors can detect glucose levels with high sensitivity and selectivity. This avoids the use of invasive blood sampling and allows for continuous monitoring of glucose levels. These can be functionalised and integrated into wearable devices, or implanted sensors, making it convenient and reliable to monitor and to be able to optimum insulin therapy. Moreover, nanoparticle-based approaches show potential in tissue regeneration, aiding insulin production restoration. For example, in particular, nanomedicine is a promising tool in theranostics of chronic kidney disease (CKD), where one radioactive drug can diagnose and a second delivers the therapy. The conventional procedure to assess renal fibrosis is by taking a kidney biopsy, which is then followed by a histopathological assessment. This method is risky, invasive, and subjective, and less than 0.01 % of kidney tissue is examined which results in diagnostic errors, limiting the accuracy of the current screening method. The standard use of pharmaceuticals has been promising but can cause hypoglycaemia, diuresis, and malnutrition because of the low caloric intake. Nanoparticles offer a new approach to both diagnosis and treatment and are an attractive candidate for managing CKD as they can carry drugs and enhance image contrast, controlling the rate and location of drug release. In the treatment of this multifaceted disease, nanoparticle delivery systems seem to be a promising and innovative therapeutic strategy, with the variety in the methods of delivery. The range of solutions that are currently being developed are promising, from enhancing the drug delivery to monitoring the glucose level, to direct tissue regeneration. There is immense potential for the advancement of nanomedicines, helping improve patient outcomes, the treatment efficacy, and allowing the alleviation of the burden and side effects of the disorder. With ongoing efforts and innovation, the future treatment of diabetes can be greatly helped with the use of nanoparticles, and these advancements will improve strategies for the management and future treatment of diabetes. Written by Saanchi Agarwal Related articles: Pre-diabetes / Can diabetes mellitus become an epidemic? / Nanomedicine / Nanoparticles on gut health / Nanogels / Nanocarriers REFERENCES Lemmerman LR, Das D, Higuita-Castro N, Mirmira RG, Gallego-Perez D. Nanomedicine-Based Strategies for Diabetes: Diagnostics, Monitoring, and Treatment. Trends Endocrinol Metab. 2020 Jun;31(6):448-458. doi: 10.1016/j.tem.2020.02.001. Epub 2020 Mar 4. PMID: 32396845; PMCID: PMC7987328. Dehghani P, Rad ME, Zarepour A, Sivakumar PM, Zarrabi A. An Insight into the Polymeric Nanoparticles Applications in Diabetes Diagnosis and Treatment. Mini Rev Med Chem. 2023;23(2):192-216. doi: 10.2174/1389557521666211116123002. PMID: 34784864. Luo XM, Yan C, Feng YM. Nanomedicine for the treatment of diabetes-associated cardiovascular diseases and fibrosis. Adv Drug Deliv Rev. 2021 May;172:234-248. doi: 10.1016/j.addr.2021.01.004. Epub 2021 Jan 5. PMID: 33417981. L. Tillman, T. A. Tabish, N. Kamaly, A. El-Briri F, C. Thiemermann, Z. I. Pranjol and M. M. Yaqoob, Review Advancements in nanomedicines for the detection and treatment of diabetic kidney disease, Biomaterials and Biosystems, 2022, 6, 100047. J. I. Cutler, E. Auyeung and C. A. Mirkin, Spherical nucleic acids, J Am Chem Soc, 2012, 134, 1376–1391. Veiseh, O., Tang, B., Whitehead, K. et al. Managing diabetes with nanomedicine: challenges and opportunities. Nat Rev Drug Discov 14, 45–57 (2015). https://doi.org/10.1038/nrd4477 Project Gallery

A short exploration of the genetic predisposition behind human behaviours Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can we blame our genes for excessive smoking and drinking? 07/05/26, 19:37 Last updated: Published: 13/01/24, 15:33 A short exploration of the genetic predisposition behind human behaviours The advancing research on how tobacco, alcohol addictions, and other detrimental behaviors are consequences of complex interplays between genetic and environmental factors has gradually developed and gained credibility. A collaborative effort involving over 100 international scientists, including researchers from the National Institutes of Health (NIH) and the National Institute on Drug Abuse (NIDA), embarked on a genome-wide association study (GWAS) to explore the heritable traits associated with tobacco and alcohol addiction. The study analyzed data from a sample size of 1.2 million biobanks, epidemiological research, and genetic testing companies, shedding light on the relationship between genetics and addiction behaviors. Researchers discovered that phenotypes related to smoking, such as when individuals began smoking habits, are genetically correlated with various diseases. In contrast, increased genetic risk for alcohol consumption is linked to reduced risk of many diseases. Previous studies pinpointed 10 genes involved in the risk of tobacco and alcohol addiction. In addition, this study further contributed to genetic links by identifying more than 400 locations in the genomes with over 500 variants associated with critical functions involving dopamine regulation, glutamate transmission and acetylcholine activation in the brain. Another study involving 3.4 million people with diverse ancestries suggested that approximately 3,823 genetic variants may impact addiction behaviors, with specific variants associated with the age at which individuals start smoking and the number of cigarettes or alcoholic drinks consumed. These studies could indicate a future where genetic screening for genes relevant to addiction behaviors is available, and this could be especially useful for those with relatives involved in certain addictions. Furthermore, it also provides perspective on whether certain genes can increase the likelihood of addiction to illegal drugs like cocaine, heroin or MDMA. However, increasing people’s awareness of whether they are at risk of developing addictions may be insufficient in deterring them from pursuing risky behaviors, which suggests that genetic screening for these genes would be beneficial as an optional screening assessment for individuals. While the influence of environmental and social factors on tobacco and alcohol addictions has long been acknowledged and explored, these studies underscore the significant role genetics plays in determining an individual’s susceptibility to nicotine and alcohol dependence. The prospect of predicting a person’s risk of addiction can lead to early interventions. Furthermore, it prevents countless health-related fatalities associated with smoking and alcoholic beverages. This primary prevention provides a different aspect to risk factors for smoking and alcohol addiction while also reducing the burden of these highly prevalent public health concerns. Written by Maya El Toukhy Related articles: Smoking cessation / Smoking and trigeminal neuralgia References: New Scientist (n.d.). Thousands of genetic variants may influence smoking and alcohol use. [online] New Scientist. Available at: https://www.newscientist.com/article/2350516thousandsofgenetic-variants-may-influence-smoking-and-alcohol-use/ [Accessed 23 Oct. 2023]. Today’s Clinical Lab. (n.d.). Do Your Genes Predispose You to Smoking and Drinking? [online] Available at: https://www.clinicallab.com/do-your-genes-predispose-you-tosmokinganddrinking-26963 [Accessed 23 Oct. 2023]. University of Minnesota. (2019). Hundreds of genes affecting tobacco and alcohol use discovered. [online] Available at: https://twin-cities.umn.edu/newsevents/hundredsgenesaffecting-tobacco-and-alcohol-use-discovered [Accessed 23 Oct. 2023]. Schlaepfer, I., Hoft, N. and Ehringer, M. (2008). The Genetic Components of Alcohol and Nicotine Co-Addiction: From Genes to Behavior. Current Drug Abuse Reviewse, 1(2), pp.124– 134. doi: https://doi.org/10.2174/1874473710801020124 . Project Gallery

Unlocking the mystery of spinal disorders and paving the way for targeted therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unveiling the cancer magnet: vertebral stem cells and spinal tumour metastasis Last updated: 29/05/25, 11:46 Published: 24/04/25, 08:00 Unlocking the mystery of spinal disorders and paving the way for targeted therapies Introduction Researchers at Weill Cornell Medicine have discovered that the vertebral bones in the spine contain a unique type of stem cell that secretes a protein-promoting tumour metastasis. This protein, called MFGE8, plays a significant role in attracting tumours to the spine, making it more susceptible to metastasis when compared to other bones in the body. A new line of research on spinal disorders This groundbreaking study , published in the journal Nature, sheds light on the mechanisms behind the preference for solid tumours to spread to the spine. The findings open up a new line of research on spinal disorders, potentially leading to a better understanding and treatment of bone diseases involving the spine. Identifying vertebral stem cells The researchers began their study by isolating skeletal stem cells, which are responsible for bone and cartilage formation, from various bones in lab mice. Through gene activity analysis, they identified a distinct set of markers for vertebral stem cells. Further experiments in mice and lab-dish cell culture systems confirmed the functional roles of these stem cells in forming spinal bone. Unravelling the mystery of spinal tropism Previous theories attributed the spine's susceptibility to metastasis to patterns of blood flow. However, the study's findings challenged this long-standing belief. Animal models reproduced the phenomenon of spinal tropism, but the researchers discovered that blood flow was not the sole explanation. Instead, they found evidence pointing towards vertebral stem cells as the possible culprits. The role of MFGE8 The researchers discovered that spinal tropism is largely a result of the protein MFGE8, which vertebral stem cells secrete in greater quantities than other bone stem cells. Removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and other long bones. Implications for cancer patients These findings have significant implications for cancer patients, particularly those at risk of spinal metastasis. The researchers are now exploring methods to block the activity of MFGE8, aiming to reduce the risk of tumour spread to the spine. By understanding the distinctive properties of vertebral stem cells, researchers hope to develop targeted treatments for spinal disorders. A new frontier in orthopaedics According to study senior author Matthew Greenblatt, the identification of these unique stem cells opens up a new subdiscipline in orthopaedics called spinal orthopaedics. Many conditions in this clinical category may be attributed to the properties of vertebral stem cells. Further research in spinal orthopaedics is needed to understand how these distinct properties of vertebral stem cells contribute to spinal disorders. The discovery of MFGE8, a protein secreted in higher amounts by vertebral stem cells, has shed light on the mechanism behind the preferential spread of tumours to the spine. By investigating methods to block MFGE8, researchers hope to reduce the risk of spinal metastasis in cancer patients. Additionally, the study findings highlight the importance of understanding the role of vertebral stem cells in bone diseases that primarily affect the spine. This new line of research may provide insights into the development of novel treatments for spinal disorders. Conclusion In conclusion, the study by researchers at Weill Cornell Medicine has shown that vertebral bones, which make up the spine, contain a particular type of stem cell that secretes a protein known as MFGE8. This protein plays a significant role in promoting tumour metastases, explaining why solid tumours often spread to the spine. The findings have opened up new avenues of research in understanding spinal disorders and may lead to the development of strategies for reducing the risk of spinal metastasis in cancer patients. Overall, this study highlights the importance of vertebral stem cells in contributing to spinal disorders and emphasises the need for further investigation in this field. Written by Sara Maria Majernikova Related articles: Cancer metastasis / Brain metastasis / Stem cells REFERENCE Sun, J., Hu, L., Bok, S. et al. A vertebral skeletal stem cell lineage driving metastasis. Nature 621, 602–609 (2023). https://doi.org/10.1038/s41586-023-06519-1 Project Gallery

Recombinant adeno-associated viruses (rAAVs) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link What you should know about rAAV gene therapy 14/07/25, 16:13 Last updated: Published: 01/10/23, 20:45 Recombinant adeno-associated viruses (rAAVs) Curing a disease with one injection: the dream, the hope, the goal of medicine. Gene therapy brings this vision to reality by harnessing viruses into therapeutic tools. Among them, adeno-associated viruses (AAVs) are the most used: genetically modified AAVs, named recombinant AAVs (rAAVs), are already used in six gene therapies approved for medical use. Over 200 clinical trials are ongoing. AAV, a virus reprogrammed to cure diseases Gene therapy inserts genetic instructions into a patient to correct a mutation responsible for a genetic disorder. Thanks to genetic engineering, researchers have co-opted AAVs (along with adenoviruses, herpes simplex viruses and lentiviruses) into delivering these instructions. Researchers have swapped the genes that allow AAVs to jump from person to person with genes to treat diseases. In other words, the virus has been genetically reprogrammed into a vector for gene transfer. The gene supplemented is referred to as transgene. Biology of AAVs AAVs were discovered in the 1960s as contaminants in cell cultures infected by adenoviruses, a coexistence to which they owe their name. AAVs consist of a protein shell (capsid) wrapped around the viral genome, a single strand of DNA long approximately 4,700 bases (4.7 kb). The genome is capped at both ends by palindromic repetitive sequences folded into T-shaped structures, the Inverted Tandem Repeats (ITRs). Sandwiched between the ITRs, four genes are found. They determine capsid components ( cap ) and capsid assembly ( aap ), genome replication ( rep ) and viral escape from infected cells ( maap ) ( Figure 1, top panel ). The replacement of these four genes with a transgene of therapeutic use and its expression by infected cells (transduction) lie at the heart of gene therapy mediated by rAAVs. Transgene transfer by rAAVs Researchers favour rAAVs as vectors because AAVs are safe (they are not linked to any disease and do not integrate into the genome), they can maintain the production of a therapeutic gene for over ten years and infect a wide range of tissues. In an rAAV, the ITRs are the only viral element preserved. The four viral genes are replaced by a therapeutic transgene, and regulatory sequences to maximise its expression. Therefore, an rAAV contains the coding sequence of the transgene, an upstream promoter to induce transcription and a downstream regulatory sequence (poly-A tail) to confer stability to the mRNA molecules produced ( Figure 1, bottom panel ). Steps of rAAV production Based on the disease, rAAVs can be administered into the blood, an organ, a muscle or the fluid bathing the central nervous system (cerebrospinal fluid). rAAVs dock on target cells via a specific interaction between the capsid and proteins on the cell surface that serve as viral receptors and co-receptors. The capsid mainly dictates which cell types will be infected (cell tropism). Upon binding, the cell engulfs the virus into membrane vesicles (endosomes) typically used to digest and recycle material. The rAAVs escape the endosomes, avoiding digestion, and enter the nucleus, where the capsid releases the single-strand DNA (ssDNA) genome, a process known as uncoating. The ITRs direct the synthesis of the second strand to reconstitute a double-strand DNA (dsDNA), the replication of the viral genome and the concatenation of individual genomes into larger, circular DNA molecules (episomes) that can persist in the host cell for years. Nuclear proteins transcribe the transgene into mRNAs; mRNAs are exported in the cytoplasm where they are translated into proteins. The rAAV has achieved successful transduction : the transgene can start exerting its therapeutic effects. A simplified overview of rAAV transduction is presented in Figure 2 . The triumphs of rAAV gene therapies rAAV gene therapies are improving lives and saving patients. Unsurprisingly, the most remarkable examples of this come from the drugs already approved. Roctavian is an rAAV gene therapy for haemophilia A, a life-threatening bleeding disorder in which the blood does not clot properly because the body cannot produce the coagulation Factor VIII. In a phase III clinical trial, Roctavian reduced bleeding rates by 85% and most treated patients (128 out of 134) no longer needed regular administration of Factor VIII, the standard therapy for the disease, for up to two years after treatment. Similar impressive results were noted for the rAAV Hemgenix, a gene therapy for haemophilia B (a bleeding disorder caused by the absence of the coagulation Factor IX). Hemgenix reduced bleeding rates by 65% and most treated patients (52 out of 54) no longer needed regular administration of Factor IX, for up to two years. The benefits of Zolgensma are even more awe-inspiring. Zolgensma is an rAAV gene therapy for spinal muscular atrophy (SMA), a genetic disorder in which neurons in the spinal cord die causing muscles to waste away irreversibly. The life expectancy of SMA patients can be as short as two years, therefore timing is critical. As a consequence, Zolgensma had to be tested in neonates: babies with the most severe form of SMA were dosed with the drug before six weeks of age and symptoms onset (SPRINT study). After 14 months, all 14 treated babies were alive and breathing without a ventilator, whilst only a quarter of untreated babies did. After 18 months, all 14 could sit without help, an impossible feat without Zolgensma. These and other resounding achievements are fuelling research on rAAVs gene therapies. Current limitations Scientists still have some significant hurdles to overcome : ● Packaging capacity: AAVs can fit in their capsids relatively short DNA sequences, which do not allow the replacement of many long genes associated with genetic disorders, ● Immunogenicity: 30-60% of individuals have antibodies against AAVs, which block rAAVs and prevent transduction, ● Tissue specificity: rAAVs often infect tissues which are not the intended target (e.g., inducing the expression for a transgene to treat a neurological disease in the liver rather than in neurons). Gene therapies, not only those delivered by rAAVs, face an additional challenge, this one only partially of a technological nature: their price tags. Their prices – rAAVs range from $850,000 (£690,000) to $3,500,000 (£2,850,000) – make them inaccessible for most patients. A cautionary tale is already out there: Glybera, the first rAAV gene therapy approved for medical use, albeit only in Europe (2012), was discontinued in 2017 because it was too expensive. Research is likely to reduce the exorbitant manufacturing costs , but the time may have come to reconsider our healthcare systems. Notes One non-viral vector exists , but its development lags behind the viral vector . Glybera for treating lipoprotein lipase deficiency, Luxturna for Leber congenital amaurosis, Zolgensma for spinal muscular atrophy, Roctavian for haemophilia A, Hemgenix for haemophilia B, and Elevidys for Duchenne muscular dystrophy. Written by Matteo Cortese, PhD Related articles: Germline gene therapy (GGT) / A potential treatment for HIV / Rabies / Antiretroviral therapy Project Gallery

Role of neurotransmitters in depression Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Inside out: the chemistry of depression Last updated: 19/02/26, 19:35 Published: 05/06/25, 08:00 Role of neurotransmitters in depression This is Article 2 in a series on psychiatric disorders and the brain. Next article: The promising effects of magic mushrooms for depression . Previous article: What does depression do to your brain? Ever wondered what’s going on inside your brain when you’re feeling down? Imagine the scene from Inside Out , where Sadness takes over the control room, overshadowing the other emotions. That’s actually not too far from what happens during depression, but the changes in your brain are much more than just a battle of emotions. Depression is the most common mental illness globally. It is typically marked by a persistently low mood and energy, and a loss of interest or pleasure in everyday activities. Risk factors include chronic stress, traumatic life events, genetic vulnerability, ageing, and female sex. While these influences are widely recognised, have you ever thought about what is actually happening inside your brain when you're depressed? You've probably heard phrases like “I need a serotonin boost,” but what does that really mean? What is serotonin, and how does it influence our emotions and mental health? What are neurotransmitters? Think of neurotransmitters as messenger pigeons between neurons. They are involved in communication between different neurons. Communication between neurons is called synaptic transmission. In synaptic transmission, neurotransmitters are released from vesicles in one neuron into the synaptic cleft (the gap between two neurons) and then bind to receptors on the receiving neuron. This is how information travels through the brain, allowing us to think, feel, and act. Serotonin is an example of a neurotransmitter. Others include dopamine, noradrenaline, acetylcholine. The monoamine theory of depression One of the most widely supported explanations for the neurobiology of depression is the monoamine theory. This theory suggests that depression results from an imbalance or deficiency of monoamines in the brain. Monoamines are a group of neurotransmitters, including serotonin, dopamine, and noradrenaline, that are synthesised from the amino acids L-tryptophan and L-tyrosine. Fun fact: Did you know around 95% of the body's serotonin is produced in the gut? This is why there is growing interest in the gut-brain axis in mental health! Different neurotransmitter systems are involved in depression and even everyday emotion processing and regulation. The dopamine (DA) system plays a key role in experiencing reward and pleasure, often linked to feelings of joy. In contrast, the serotonin (5-HT) system is more associated with responses to punishment and aversive experiences, such as sadness or disgust. Noradrenaline (NE), on the other hand, is closely tied to fear, anger, and the activation of the "fight or flight" response during stressful situations. These neurotransmitters are thought to underlie three fundamental emotional states, which can combine in different ways to form a wide range of complex emotions. In the brain, these monoamines regulate mood, motivation, pleasure, and emotional stability. When levels are low, people may experience sadness, fatigue, apathy, and changes in appetite or sleep. This is why many antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), aim to increase the availability of these monoamines in the synapse, improving communication between neurons and, over time, alleviating symptoms. SSRI treatment, in particular, is based on the serotonin hypothesis, a subset of the broader monoamine theory of depression, which suggests that reduced serotonin levels contribute to depressive symptoms. Conclusion: why depression is more than a mood Depression isn’t just “feeling sad”; it is a real condition that involves real chemical changes in the brain. The monoamine theory helps explain this by focusing on key neurotransmitters like serotonin, dopamine, and noradrenaline, which help control mood, motivation, and emotional balance. When these chemicals are out of sync, too low or not working properly, it can lead to the emotional numbness, low energy, and hopelessness that many people with depression experience. These neurotransmitters do not work in isolation; they influence how we respond to rewards, stress, and even daily activities. By understanding the biological changes behind depression, we take an important step toward not only understanding the condition but also reducing the stigma around it. Written by Chloe Kam Related articles: Emotional chemistry / Embarrassment / Postpartum depression in adolescent mothers REFERENCES Barchas, J.D. and Altemus, M. (1999) ‘Monoamine Hypotheses of Mood Disorders’, in Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition . Lippincott-Raven. Available at: https://www.ncbi.nlm.nih.gov/books/NBK28257/ (Accessed: 3 May 2025). Jiang, Y. et al. (2022) ‘Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders’, Pharmaceuticals , 15(10), p. 1203. Available at: https://doi.org/10.3390/ph15101203 . Project Gallery

Unraveling the mysteries of protein-DNA interactions Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Zinc fingers in action 14/07/25, 16:21 Last updated: Published: 07/01/24, 14:22 Unraveling the mysteries of protein-DNA interactions Zinc-finger proteins are one of the most prevalent proteins used in DNA-binding motifs in biological processes. They are common as eukaryotic transcriptional factors. As they are structurally diverse, they interact in cellular processes like RNA packaging, DNA recognition, and transcriptional activation. Cys2His2 zinc- finger proteins are significant in cellular processes because of their short helical structure. The motif forms from a few amino acid sequences that contain cysteine and histidine residues that coordinate to a zinc ion. The zinc ions are crucial in stabilising the protein during folding. They also hold the α-helix and β-sheetstructures in place. The protein’s stability comes from the weak hydrophobic core and zinc coordination created by chelating. The zinc-finger/DNA complex is formed from the fingers interacting with up to four bases. The zinc finger DNA complex was first discovered from the transcription factor TFIIIA. The transcription factor had a ninefold pattern containing hydrophobic residues, histidine, and cysteine. The zinc finger motif was then concluded to consist of thirty amino acids and have a DNA binding domain with a zinc ion. This was confirmed by an extended x-ray absorption fine structure analysis. It was concluded that the contacts between the DNA strand and α helix occur due to hydrogen bonding and Van der Waals interactions. From these studies, the structures of zinc finger domains play vital roles in many processes other than DNA binding. Their tertiary structure allows the proteins to act as DNA-binding motifs. The alpha helix functions as the protein recognition component by inserting the protein into the main groove of DNA. Immobilizing zinc-finger proteins on a polymer chip can be used as an example to identify infections in the human body. This section provides a summary of the many kinds of DNA recognition and the generic protein-folding principles. Firstly, a specific binding site probe is needed to identify the DNA sequence region. This allows the identification of specific base pairs in the sequence. The hydrogen bonds between the amino acids in the zinc-finger proteins and DNA bases allow the zinc- finger proteins to bind to non-specific backbone phosphates. The non-specific backbone phosphates are formed from the interactions in the major and minor grooves of the DNA. The zinc-finger DNA interactions contribute substantially to hydrogen bonding and overall binding energy. To conclude, zinc fingers are very common structural motifs that are used as model systems to investigate how these proteins can recognise DNA sequences. This research has been involved in developing important therapeutic tools. Their unique structure allows them to be heavily involved in DNA binding, most commonly the Cys2His2 fingers. These binding interactions can be further explored to understand how certain target genes are bound to or how inhibitors can show the pharmacological properties of the zinc finger proteins. Written by Anam Ahmed Related articles: p53 protein / Anti-freeze proteins Project Gallery

In bones, neural communications, fertilisation and more Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The importance of calcium in life Last updated: 12/03/25, 16:45 Published: 10/04/25, 08:00 In bones, neural communications, fertilisation and more Did you know that the same mineral that gives your bones strength also helps to maintain your heartbeat and even plays a role in the very start of life? Calcium, the most abundant mineral in the human body, is primarily found in bones and teeth as calcium phosphate (Ca₃(PO₄)₂). But beyond its structural role, calcium ions are essential for nearly every biological function, from muscle contractions to nerve signalling. What makes calcium so versatile, while other minerals like iron, have far more limited roles? To truly understand its significance, we must explore its underlying chemical properties. Calcium and bones The calcium ion carries a 2+ charge allowing it to form stronger ionic bonds and interact strongly with negatively charged molecules like nucleotides and ATP. This makes it essential for energy transfer in cells. In comparison to monovalent ions like Na+ and K+, calcium, therefore, has a more significant charge density, increasing affinity for anions. However, the ion also has more shells than beryllium and magnesium in the same group (Group 2), contributing to reduced charge density. These properties are very crucial in determining the strength of Calcium compounds, as a high charge density may result in problems with toxicity and difficulty in the breakdown of the product. Calcium phosphate exists as hydroxyapatite in bones and teeth, giving them hardness and rigidity. Hydroxyapatite forms hexagonal crystals that are tightly packed, contributing to the dense, durable structure of bones. These crystals are organised into a matrix along collagen fibres, creating a composite material that combines rigidity (from hydroxyapatite) and flexibility (from collagen). The properties of hydroxyapatite make it uniquely suited for its roles in the body. Its hardness provides bones with the ability to resist deformation and compression, while its porous structure allows space for blood vessels, bone marrow, and the exchange of nutrients and waste. Osteoclasts break down the bone releasing calcium and phosphate ions while osteoblasts can reabsorb this calcium to reform bones in another area of the body, maintaining skeletal health and strength. Neural communication Imagine a relay race where one runner must pass the baton to the next for the race to continue. In a similar way, calcium ions act as messengers in the nervous system, triggering the release of neurotransmitters which allow nerve cells to communicate with each other. Upon experiencing a stimulus, sodium ions begin to enter neurones through voltage-gated sodium channels, causing depolarisation, which sends an electrical signal throughout the neurone that results in the opening of other sodium channels, carrying the electrical signal throughout the neurone until the signal reaches the axon terminal. When the action potential reaches the axon terminal, it triggers the opening of voltage-gated calcium channels in the membrane of the presynaptic neurone. Calcium ions from the extracellular fluid flow into the neurone due to the concentration gradient. This influx of calcium ions is a critical step in neural communication, as it directly facilitates the release of neurotransmitters stored in synaptic vesicles. This action helps to coordinate the strength and the timing of each heartbeat. Calcium ions bind to proteins on the surface of these vesicles, which enables the vesicles to fuse with the presynaptic membrane. This fusion releases neurotransmitters, such as acetylcholine, into the synaptic cleft—a tiny gap between the presynaptic and postsynaptic neurones. These neurotransmitters then bind to specific receptors on the postsynaptic neurone, leading to either an excitatory or inhibitory response. For example, acetylcholine often causes an excitatory response, such as muscle contraction or memory formation. Fertilisation Calcium ions are crucial for fertilisation, facilitating key events from sperm-egg interaction to the activation of embryonic development. When a sperm binds to the egg’s outer layer, calcium ions trigger the release of enzymes from the sperm, enabling it to penetrate the egg. Following the sperm-egg fusion, calcium ions are released within the egg, creating a wave-like signal. The rise in intracellular calcium levels in the egg has several critical effects triggers the cortical reaction, in which cortical granules – small vesicles located beneath the egg’s plasma membrane- release their contents into the space between the plasma membrane and the zona pellucida. The enzymes released during this reaction modify the zona pellucida, making it impermeable to other sperm. This process prevents polyspermy, ensuring that only one sperm fertilises the egg. This precise calcium signalling achieves successful fertilisation and the initiation of new life. Role of calcium in other organisms Calcium is a vital element essential for initiating and sustaining human life, but its importance extends far beyond the human body. Its role is not confined to animals as calcium is equally critical in the physiology of plants and fungi, where it contributes to a wide range of biological processes. In plants, calcium ions are used to form calcium pectate, a chemical used to strengthen the cell walls of the cell and make plant cells stick together. Additionally, calcium is vital for root development and nutrient uptake. It helps in the formation of root nodules in legumes, where nitrogen-fixing bacteria establish symbiotic relationships, and it influences the movement of ions across cell membranes to regulate nutrient transport. Furthermore, calcium oscillations play a crucial role in regulating the polarised growth of fungal hyphae, which are essential for environmental exploration and host infection. Hyphal growth is characterised by a highly localised expansion at the tip, requiring cytoplasmic movement and continuous synthesis of the cell wall. Calcium ions are central to these processes, functioning as dynamic signalling molecules. Calcium concentration is highest at the growing hyphal tip, forming a steep gradient essential for maintaining growth direction. This gradient is not static but oscillatory, with periodic fluctuations in cytosolic calcium levels. These oscillations arise from the interplay of calcium influx through plasma membrane channels like voltage-gated channels. These are critical for coordinating key processes at the hyphal tip. Calcium regulates vesicle trafficking by triggering the fusion of vesicles carrying enzymes with the plasma membrane. Additionally, calcium modulates the actin cytoskeleton, which provides tracks for vesicle transport and maintains the structural polarity of the hypha. Periodic calcium signals promote the dynamic assembly and disassembly of actin filaments, ensuring flexibility and responsiveness to physical barriers to mobility during growth. Through its oscillatory signalling, calcium enables the precise regulation required for hyphal growth and network formation. Conclusion In conclusion, calcium is a remarkably versatile element, playing vital roles across a diverse range of organisms. In humans and animals, it not only provides structural integrity through bones and teeth but also regulates critical physiological processes such as nerve signalling. Beyond animal systems, calcium is also essential in plants, where it strengthens cell walls and improves structure. In fungi, calcium oscillations are fundamental to hyphal growth, coordinating vesicle trafficking. From building bones to driving vital biological processes, calcium is a silent powerhouse in life. Its influence stretches across humans, plants, and even fungi. Its role is truly indispensable. Written by Barayturk Aydin Related articles: Bone cancer / Tooth decay REFERENCES Haider, A. et al. (2017) Recent advances in the synthesis, functionalization and biomedical applications of Hydroxyapatite: A Review, RSC Advances. Available at: https://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra26124h (Accessed: 24 November 2024). Splettstoesser, T. (2024) Action potentials and synapses, Queensland Brain Institute - University of Queensland. Available at: https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials-and-synapses (Accessed: 01 December 2024). Abbott, A., L. (2001) ‘Calcium and the control of mammalian cortical granule exocytosis’, Frontiers in Bioscience, 6(1), p. d792. doi:10.2741/abbott. Vaz Martins, T. and Livina, V.N. (2019) What drives symbiotic calcium signalling in legumes? insights and challenges of imaging, International journal of molecular sciences. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6539980/#:~:text=Currently%2C%20two%20different%20calcium%20signals,formation%20of%20the%20root%20nodule%2C (Accessed: 01 December 2024). Lew, R.R. (2011) ‘How does a hypha grow? the biophysics of pressurized growth in fungi’, Nature Reviews Microbiology, 9(7), pp. 509–518. doi:10.1038/nrmicro2591. Project Gallery

The effect on sleep on nutrition (nutrition timing) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The interaction between circadian rhythms and nutrition Last updated: 27/04/25, 12:20 Published: 01/05/25, 08:00 The effect on sleep on nutrition (nutrition timing) The circadian system regulates numerous biological processes with roughly a 24-hour cycle, helping the organism adapt to the day-night rhythm. Among others, circadian rhythms regulate metabolism, energy expenditure, and sleep, for which meal timing is an excellent inducer. Evidence has shown that meal timing has a profound impact on health, gene expression, and lifespan. Proper timed feeding in accordance with the natural circadian rhythms of the body might improve metabolic health and reduce chronic disease risk. Circadian rhythms Circadian rhythms are controlled by the central clock of the brain, which coordinates biological functions with the light-dark cycle. Along with meal timing, circadian rhythms influence key elements of metabolism such as insulin sensitivity, fat storage, and glucose metabolism. When meal timing is not synchronised with the body's natural rhythm, it can cause circadian misalignment, disrupting metabolic processes and contributing to obesity, diabetes, and cardiovascular diseases. Literature has indicated that one should eat best during the daytime, particularly synchronised with the active phase of the body. Eating late at night or in the evening when the circadian rhythm of the body is directed towards sleep could impair metabolic function and lead to weight gain, insulin resistance, and numerous other diseases. Also, having larger meals in the morning and smaller meals later in the evening has been linked to improved metabolic health, sleep quality, and even lifespan. A time-restricted eating window, in which individuals eat all meals within a approximately 10–12 hour window, holds promise for improving human health outcomes like glucose metabolism, inflammation, harmful gene expression, and weight loss ( Figure 1 ). It is necessary to consider the impact of meal timing on gene expression. Our genes react to a number of stimuli, including environmental cues like food and light exposure. Gene expression of the body's metabolic, immune, and DNA repair processes are regulated by the body's circadian clock. Disturbances in meal timing influence the expression of these genes, which may result in greater susceptibility to diseases and reduced lifespan. Certain nutrients, such as melatonin in cherries and grapes, and magnesium in leafy greens and nuts, can improve sleep quality and circadian entrainment. Omega-3 fatty acids in fatty fish and flax seeds also have been shown to regulate circadian genes and improve metabolic functions. Other species Meal timing is quite varied among species, and animals have adapted such that food-seeking behavior is entrained into circadian rhythm and environmental time cues. There are nocturnal animals which eat at night, when they are active ( Figure 2 ). These nocturnal animals have evolved to align their meal time with their period of activity to maximise metabolic efficiency and lifespan. Meal timing is optimised in these animals for night activity and digestion. Humans, and most other animals, are diurnal and consume food during the day. In these animals, consuming most of their calories during the day is conducive to metabolic processes like glucose homeostasis and fat storage. These species tend to have better metabolic health when they are on a feeding regimen that is synchronized with the natural light-dark cycle. Conclusion Meal timing is important in human health, genetics, and life expectancy. Synchronising meal times with the body's circadian rhythms optimises metabolic function, reduces chronic disease incidence, and potentially increases longevity by reducing inflammatory genes and upregulating protective ones. This altered gene expression affects the way food is metabolised and metabolic signals are acted upon by the body. Humans naturally gravitate towards eating during daytime hours, while other creatures have feeding habits that are adaptively suited to their own distinct environmental needs. It is important to consider this science and incorporate it into our schedules to receive the best outcome from an activity that we do not normally think about. Written by B. Esfandyare Related article: The chronotypes REFERENCES Meléndez-Fernández, O.H., Liu, J.A. and Nelson, R.J. (2023). Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism. International Journal of Molecular Sciences , [online] 24(4), p.3392. doi: https://doi.org/10.3390/ijms24043392 . Paoli, A., Tinsley, G., Bianco, A. and Moro, T. (2019). The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting. Nutrients , [online] 11(4), p.719. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30925707 . Potter, G.D.M., Cade, J.E., Grant, P.J. and Hardie, L.J. (2016). Nutrition and the circadian system. British Journal of Nutrition , [online] 116(3), pp.434–442. doi: https://doi.org/10.1017/s0007114516002117 . St-Onge MP, Ard J, Baskin ML, et al. Meal timing and frequency: implications for obesity prevention. Am J Lifestyle Med. 2017;11(1):7-16. Patterson RE, Sears DD. Metabolic effects of intermittent fasting. Annu Rev Nutr. 2017;37:371-393. Zhdanova IV, Wurtman RJ. Melatonin treatment for age-related insomnia. Endocrine. 2012;42(3):1-12. Prabhat, A., Batra, T. and Kumar, V. (2020). Effects of timed food availability on reproduction and metabolism in zebra finches: Molecular insights into homeostatic adaptation to food-restriction in diurnal vertebrates.Hormones and Behavior, 125, p.104820. Project Gallery

The concept of memory erasure is huge and complex Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can you erase your memory? 09/07/25, 14:31 Last updated: Published: 23/11/23, 11:08 The concept of memory erasure is huge and complex What is memory? Our brain is a wiggly structure in our skull, made up of roughly 100 billion neurones. It is a wondrous organ, capable of processing 34 gigabytes of digital data per day, yet being able to retain information, and form memory – something that many would argue, defines who we are. So.. what is memory? And how does our brain form them? Loosely defined, memory is the capacity to store and retrieve information. There are three types of memory: short-term, working, and long-term memory (LTM). Today, we will be focusing on LTM. In order to form LTM, we need to learn and store memory. This follows the process of encoding, storage, retrieval, and consolidation. In order to understand the biochemical attributes of memory in our brain, a psychologist, Dr Lashley, conducted extensive experiments on rats to investigate if there were specific pathways in our brain that we could damage to prevent memory from being recalled. His results showed that despite large areas of the brain being removed, the rats were still able to perform simple tasks ( Figures 1-2 ). Lashley’s experiment transformed our understanding of memory, leading to the concept of “engrams”. Takamiya et al., 2020 defines “memory engrams” as traces of LTM consolidated in the brain by experience. According to Lashley, the engrams were not localised in specific pathways. Rather, they were distributed across the whole of the brain. Can memory be erased? The concept of memory erasure is huge and complex. In order to simplify this, let’s divide them into two categories: unintentional, and intentional. Let’s take amnesia for example. This is a form of unintentional memory ‘erasure’. There are two types of amnesia: retrograde amnesia, and anterograde amnesia. Retrograde amnesia is the loss of memory that was formed before acquiring amnesia. On the other hand, anterograde amnesia is the inability to make new memories since acquiring amnesia. Typically, a person with amnesia would exhibit both retrograde, and anterograde amnesia, but at different degrees of severity ( Figure 3 ). Can we ‘erase’ our memory intentionally? And how would this be of use to us? This is where things get really interesting. Currently, the possibility of intentional memory ‘erasure’ is being investigated in patients for the treatment of post-traumatic stress disorder (PTSD). In these clinical trials, patients with PTSD are given drugs that block these traumatic memories. For example, propranolol, an adrenergic beta receptor blocker impairs the acquisition, retrieval, and reconsolidation of this memory. Incredible, isn’t it? Although this is not the current standard treatment for PTSD, we can only imagine how relieving it would be for our fellow friends who suffer from PTSD if their traumatic memories could be ‘erased’. However, with every step ahead, we must always be extremely cautious. What if things go wrong? We are dealing with our brain, arguably one of the most important organs in our body after all. Regardless, the potential for memory ‘erasure’ in treating PTSD seems both promising and intriguing, and the complexities and ethical considerations surrounding such advancements underscore the need for careful and responsible exploration in the realm of neuroscience and medicine. Written by Joecelyn Kiran Tan Related articles: Synaptic plasticity / Boom, and you're back! (intrusive memories) / Sleep and memory loss Project Gallery