Search Index

Recent prospects for carbon monoxide indicate so Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can carbon monoxide unlock new pathways in inflammation therapy? 20/03/25, 12:03 Last updated: Published: 01/09/24, 10:31 Recent prospects for carbon monoxide indicate so Carbon monoxide (CO) is a colourless, odourless and tasteless gas which is a major product of the incomplete combustion of carbon-containing compounds. The toxic identity CO stems from its strong affinity for the haemoglobin in our blood which is around 300 times as strong as the affinity of oxygen. As a result, once the gas is inhaled, CO binds to the haemoglobin instead and reduces the amount of oxygen our blood can transport, which can cause hypoxia (low levels of oxygen in tissue) and dizziness, eventually leading to death. However, an intriguing fact is that CO is also endogenously produced in our body, due to the degradation of haem in the blood. Moreover, recent prospects for CO indicate that it may even be developed as an anti-inflammatory drug. How CO is produced in the body See Figure 1 Haem is a prosthetic (non-peptide) group in haemoglobin, where the oxygen binds to the iron in the molecule. When red blood cells reach the end of their lifespan of around 120 days, they are broken down in a reaction called haemolysis. This occurs in the bone marrow by macrophages that engulf the cells, which contain the necessary haem-oxygenase enzyme. Haem-oxygenase converts haem into CO, along with Fe2+ and biliverdin, the latter being converted to bilirubin for excretion. The breakdown of haem is crucial because the molecule is pro-oxidant. Therefore, free haem in the blood can lead to oxidative stress in cells, potentially resulting in cancers. Haem degradation also contributes to the recycling of iron for the synthesis of new haem molecules or proteins like myoglobin. This is crucial for maintaining iron homeostasis in the body. The flow map illustrates haemolysis and the products produced, which either protect cells from further stress or result in cell injury. CO can go on to induce anti-inflammatory effects- see Figure 2 . Protein kinases and CO Understanding protein kinases is crucial before exploring carbon monoxide (CO) reactions. Protein kinases phosphorylate (add a phosphate group to) proteins using ATP. Protein kinases are necessary to signal the release of a hormone or regulating cell growth. Each kinase has two regulatory (R) subunits and two catalytic (C) subunits. ATP as a reactant is usually sufficient for protein kinases. However, some kinases require additional mitogens – specific activating molecules like cytokines (proteins regulating immune cell growth), that are involved in regulating cell division and growth. Without the activating molecules, the R subunits bind tightly to the C subunits, preventing phosphorylation. Research on obese mice showed that CO binding to a Mitogen-Activated Protein Kinase (MAPK) called p38 inhibits inflammatory responses. This kinase pathway enhances insulin sensitivity, reducing obesity effects. The studies used gene therapy, modifying haem-oxygenase levels in mice. Mice with reduced haem-oxygenase levels had more adipocytes (fat-storing cells) and increased insulin resistance, suggesting CO treatment potential for chronic obstructive pulmonary disease (COPD), which causes persistent lung inflammation and results in 3 million deaths annually. Carbon-monoxide-releasing molecules As a result of these advancements, specific CO-releasing molecules (CORMs) have been developed to release carbon monoxide at specific doses. Researchers are particularly interested in the ability of CORMs to regulate oxidative stress and improve outcomes in conditions during organ transplantation, and cardiovascular diseases. Advances in the design of CORMs have focused on improving their stability, and targeted release to specific tissues or cellular environments. For instance, CORMs based on transition metals like ruthenium, manganese, and iron have been developed to enhance their efficacy and minimize side effects. This is achieved through carbon monoxide forming a stable ‘ligand’ structure with metals to travel in the bloodstream. Under an exposure to light or a chemical, or even by natural breakdown, these structures can slowly distribute CO molecules. Although the current research did not find any notable side effects within mouse cells, this does not reflect the mechanisms in human organ systems, therefore there is still a major risk of incompatibility due to water insolubility and toxicity issues. These problems could lead to potentially lead to disruption in the cell cycle, which may promote neurodegenerative diseases. Conclusion: the future of carbon monoxide Carbon monoxide has transitioned from being a notorious toxin to a valuable therapeutic agent. Advances in CO-releasing molecules have enabled its safe and controlled use, elevating its anti-inflammatory and protective properties to treat various inflammatory conditions effectively. This shift underpins the potential of CO to revolutionise inflammation therapy. It is important to remember that while carbon monoxide-releasing molecules (CORMs) have potential in controlled therapeutic settings, carbon monoxide gas itself remains highly toxic and should be handled with extreme caution to avoid serious health risks. Written by Baraytuk Aydin Related articles: Schizophrenia, inflammation and ageing / Kawasaki disease REFERENCES Different Faces of the Heme-Heme Oxygenase System in Inflammation - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/The-colorimetric-actions-of-the-heme-HO-system-heme-oxygenase-mediated-heme-degradation_fig3_6531826 (accessed 11 Jul, 2024). Nath, K.A. (2006) Heme oxygenase-1: A provenance for cytoprotective pathways in the kidney and other tissues, Kidney International. Available at: https://www.sciencedirect.com/science/article/pii/S0085253815519595 (Accessed: 12 July 2024). Gáll, T. et al. (2020) ‘Therapeutic potential of carbon monoxide (CO) and hydrogen sulfide (H2S) in hemolytic and hemorrhagic vascular disorders—interaction between the heme oxygenase and H2S-producing systems’, International Journal of Molecular Sciences, 22(1), p. 47. doi:10.3390/ijms22010047. Venkat, A. (2024) Protein kinase, Wikipedia. Available at: https://en.wikipedia.org/wiki/Protein_kinase (Accessed: 12 July 2024). Goebel, U. and Wollborn, J. (2020) Carbon monoxide in intensive care medicine-time to start the therapeutic application?! - intensive care medicine experimental, SpringerOpen. Available at: https://icm-experimental.springeropen.com/articles/10.1186/s40635-020-0292-8 (Accessed: 07 July 2024). Bansal, S. et al. (2024) ‘Carbon monoxide as a potential therapeutic agent: A molecular analysis of its safety profiles’, Journal of Medicinal Chemistry, 67(12), pp. 9789–9815. doi:10.1021/acs.jmedchem.4c00823. DeSimone, C.A., Naqvi, S.L. and Tasker, S.Z. (2022) ‘Thiocormates: Tunable and cost‐effective carbon monoxide‐releasing molecules’, Chemistry – A European Journal, 28(41). doi:10.1002/chem.202201326. Project Gallery

Unlocking the secrets to gut health Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The power of probiotics 14/07/25, 14:59 Last updated: Published: 18/08/23, 19:58 Unlocking the secrets to gut health What are probiotics? Probiotics are dietary supplements that consist of live cultures of bacteria or yeast. In the human body, more precisely in the microbiome, there are about 4 trillion bacteria, which include almost 450 species. These bacteria are necessary for the proper functioning of the entire body, especially the intestines and digestive system. In probiotics, bacteria from the Lactobacillus and Bifidobacterium families are most often used, as well as yeasts such as Saccharomyces cerevisiae. How probiotics work? Probiotics have a wide range of effects on our body. Their main task is to strengthen immunity and improve the condition of the digestive tract. This is because microorganisms produce natural antibodies, and also constitute a kind of protective barrier that does not allow factors conducive to infection to our intestine. Types of probiotics Most often, lactic acid bacteria of the genera Lactobacillus and Bifidobacterium are used as probiotics, but some species of Escherichia and Bacillus bacteria and the yeast Saccharomyces cerevisiae boulardi also have pro-health properties. Probiotics for your gut health The composition of our bacterial flora in the intestines determines the proper functioning of the digestive and immune systems. Probiotics have a positive effect primarily on the intestinal flora. They speed up metabolism and lower bad cholesterol (LDL). Live cultures of bacteria protect our digestive system. They improve digestion, regulate intestinal peristalsis, and prevent diarrhoea. They also increase the nutritional value of products - they facilitate the absorption of minerals such as magnesium and iron as well as vitamins from group B and K. In addition, probiotics strengthen immunity and protect us from infections caused by pathogenic bacteria. Therefore, it is very important to take as many probiotics as possible during and after antibiotic treatment. They will then regenerate the intestinal flora damaged by antibiotic therapy and reduce inflammation. Main benefits · facilitate the digestive process · increase the absorption of vitamins and minerals · during antibiotic treatments, they protect our intestinal microflora · affect the immune system by increasing resistance to infections · some strains have anti-allergic and anti-cancer properties · lower cholesterol · relieve the symptoms of lactose intolerance · ability to synthesize some B vitamins, vitamin K, folic acid Written by Aleksandra Zurowska Related articles: The gut microbiome / Vitamins / Interplay of hormones and microbiome Project Gallery

Explaining and predicting the behaviour of serial killers Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The new age of forensic neurology 14/07/25, 14:58 Last updated: Published: 23/08/23, 16:16 Explaining and predicting the behaviour of serial killers Background Nobody can argue that true crime has taken the media by storm in recent years. In 2021, the search to find Gabby Petito inflamed social media, with the r/gabbypetito subreddit having 120,000 members at its peak. Tiktok ‘psychics’ would amass millions of views by attempting to predict how the case would progress, with predictably terrible results. A small solace remains, however; the fact that increased media presence of murder cases increases the rate at which research into murderers is published. The increase in both research and media attention toward true crime continued through 2022, invigorated by the release of Monster: the Dahmer Story on Netflix, which was viewed on Netflix for over 1 billion hours by its user base. It could be argued that the popularity of this show and others depicting serial killers also increased the publication of research on the neurology of serial killers. The neurological basis of the serial killer refractory period Dilly (2021) encompasses some very interesting correlational research into the neurological factors at play in the evocation of the serial killer refractory period. Following analysis of the refractory periods of ten American serial killers, a metaanalysis of prior research was performed to establish which prior theory most thoroughly explained the patterns derived. The American serial killers utilised in this investigation were: The Golden State Killer, Joseph James DeAngelo. Jeffrey Dahmer. Ted Bundy. John Wayne Gacy. The Night Stalker, Richard Ramirez. The BTK Killer, Dennis Rader. The I-5 Killer, Randall Woodfield. Son of Sam, David Berkowitz. The Green River Killer, Gary Ridgway. The Co-Ed Killer, Edmund Kemper III. Theory no. 1 While this research is purely speculative due to the lack of real-time neurological imaging of the killers both during refractory periods and their murderous rampages, this research was demonstrated to lend credence to a prior theory proposed by Simkin and Roychowdhury (2014). This research, titled Stochastic Modelling of a Serial Killer , theorised based on their own collated data that the refractory period of serial killers functions identically to that of the refractory period of neurons. This theory is based upon the idea that murder precipitates the release of a powerful barrage of neurotransmitters, culminating in widespread neurological activation. In line with neurological refractory periods, it is believed that this extreme change in state of activation is followed by a period of time wherein another global activation event cannot occur. Theory no. 2 Hamdi et al. (2022) delineates the extent to which the subject’s murderous impulses were derived from Fregoli syndrome, rather than his comorbid schizophrenia. This research elucidated how schizophrenic symptoms can synergise with symptoms of delusional identification syndromes (DIS) to create distinct behaviours and thought patterns that catalyse sufferers to engage in homicidal impulses. DIS include a range of disorders wherein sufferers experience issues identifying objects, people, places or events; Fregoli Syndrome is a DIS characterised by the delusional belief that people around the sufferer are familiar figures in disguise. The subject’s Fregoli Syndrome caused the degeneration of his trust of those around him, which quickly led to an increase in aggressive behaviours. The killer attacked each member of his family multiple times before undertaking his first homicide- excluding his father, whom reportedly ‘scared him very much’. Unsurprisingly then, his victim cohort of choice for murder were older men. The neurobiological explanation of Fregoli Syndrome asserts that the impairment of facial identification, wherein cerebrocortical hyperactivity catalyses delusional identification of unfamiliar faces as familiar ones. Conclusion Forensic neurology has been a key element in expanding the understanding of serial killers, with the research of Raine et al. (1997) popularising the use of neurology to answer the many questions posed by the existence of serial killers. Since Raine, Buchsbaum and LaCasse of the 1997 study first used brain scanning techniques to study and understand serial killers, the use of brain scanning techniques to study this population has become a near-perfect art, becoming ever more of a valid option for use both in understanding and predicting serial killer behaviour. In all likelihood, future innovations in forensic neurology research will continue to bring about positive change, reducing homicidal crime with the invention and use of different methods and systems to predict and stop the crimes before they happen. Summarised from a full investigation. Written by Aimee Wilson Related articles: Serial killers in healthcare / Brain of a bully Project Gallery

The yearly incidence of TBI is around 27 and 69 million people worldwide Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Beyond the bump: unravelling traumatic brain injuries 13/11/25, 12:27 Last updated: Published: 15/10/24, 11:32 The yearly incidence of TBI is around 27 and 69 million people worldwide A traumatic brain injury (TBI) is one of the most serious and complex injuries sustained by the human body, often with profound and long-term effects on an individual’s physical, emotional, behavioural and cognitive abilities. What is a traumatic brain injury? A TBI results from an external force which causes structural and physical damage to the brain. The primary injury refers to the immediate damage to the brain tissue which is caused directly by the event. Whereas secondary injuries result from the cascade of cellular and molecular processes triggered by the initial injury and develop from hours to weeks following the initial TBI. Typically, the injury can be penetrating, where an object pierces the skull and damages the brain, or non-penetrating which occurs when the external force is large enough to shake the brain within the skull causing coup- contrecoup damage. Diagnosis and severity The severity of a TBI is classified as either mild (aka concussion), moderate, or severe, using a variety of indices. Whilst more than 75% of TBIs are mild, even these individuals can suffer long-term consequences from post-concussion syndrome. Here are two commonly used measures to initially classify severity: The Glasgow Coma Scale (GCS) is an initial neurological examination which assesses severity based on the patient’s ability to open their eyes, move, and respond verbally. It is a strong indicator of whether an injury is mild (GCS 13-15), moderate (GCS 9-12) or severe (≤8). Following the injury and any period of unconsciousness, when a patient has trouble with their memory and is confused, they are said to have post-traumatic amnesia (PTA). This is another measure of injury severity and lasts up to 30 30 minutes in mild TBI, between 30 minutes and 24 hours in moderate TBI, and over 24 hours in severe TBI. Imaging tests including CT scans and MRIs are used to detect brain bleeds, swelling or any other damage. These tests are essential upon arrival to the hospital, especially in moderate and severe cases to understand the full extent of the injury. Leading causes of TBI Common causes of TBI are a result of: Falls (most common in young children and older adults) Vehicle collisions (road traffic accidents- RTAs) Inter-personal violence Sports injuries Explosive blasts Interestingly, the rate of TBI is 1.5 times more common in men than women. General symptoms The symptoms and outcome of a TBI depend on the severity and location of the injury. They differ from person to person based on a range of factors which include pre-injury sociodemographic vulnerabilities including age, sex and level of education, as well as premorbid mental illnesses. There are also post-injury factors such as access to rehabilitation and psychosocial support which influence recovery. Due to this, nobody will have the same experience of a TBI, however there are some effects which are more common than others which are described: Mild TBI: Physical symptoms: headaches, dizziness, nausea, and blurred vision. Cognitive symptoms: confusion, trouble concentrating, difficulty with memory or disorientation. Emotional symptoms: mood swings, irritability, depression or anxiety. Moderate-to-severe TBI: Behavioural symptoms: aggression, personality change, disinhibition, impulsiveness. Cognitive symptoms: difficulties with attention and concentration, decision making, memory, executive dysfunction, information processing, motivation, language, reasoning, self-awareness. Physical symptoms: headaches, seizures, speech problems, fatigue, weakness or paralysis. Many of these symptoms are ‘hidden’ and can often impact functional outcomes for an individual, such as their capacity for employment and daily living (i.e., washing, cooking, cleaning etc.). The long-term effects of TBI can vary, with some returning to normal functioning. However, others might experience lifelong disabilities and require adjustments in their daily lives. For more information and support, there are some great resources on the Headway website, a leading charity which supports individuals after brain injury. Written by Alice Jayne Greenan Related articles: Why brain injuries affect adults and children differently / Neuroimaging / Different types of seizures Project Gallery

The future of targeted cancer therapeutics Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Bioorthogonal Chemistry 04/02/25, 15:42 Last updated: Published: 01/09/24, 10:47 The future of targeted cancer therapeutics ‘Bioorthogonal chemistry’ is a term coined in 2003 by American Chemist & 2022 Nobel Prize Laureate Carolyn Bertozzi. It encompasses a set of chemical reactions which can occur within biological environments, whilst exerting minimal effect on native biomolecules or interference with native biochemical processes of the host organism - these reactions exist ‘orthogonal’ (perpendicular) to biology. Key functional groups in Bioorthogonal Chemistry include the alkynes (carbon-carbon triple bonds) and the azides (⁻N=N⁺=N⁻) . The azides are particularly bioorthogonal due to their minute size (which is favourable for cell permeability and avoiding ‘perturbations’ - the alteration of a function of a biological system), metabolic stability, and how, as they don’t naturally exist in cells, they have no competing biological side reactions. Past & present uses of bioorthogonal chemistry include: ● Vehicle airbags: Modern vehicle airbags contain sodium azide (NaN₃), a shock sensitive, explosive compound. When a vehicle’s crash sensor is triggered, an electrical charge is administered which starts the chemical reaction, inflating the air bag with harmless nitrogen gas (2NaN₃ → 2Na + 3N₂). This reaction can occur in as quickly as 0.03 seconds! ● Early HIV treatment: Azidothymidine - AZT - (Fig. 1) was the first drug used to treat HIV infection. For viruses to replicate, they use an enzyme called reverse transcriptase to convert their single-stranded RNA genome to double-stranded DNA in a process termed reverse transcription. When this antiretroviral medicine is used, instead of the virus transcribing thymidine, it instead transcribes the AZT, which contains an azide Group, thus stalling DNA synthesis of HIV and producing less viruses. Another key feature to consider when discussing uses of Bioorthogonal Chemistry are Click Reactions. Click Reactions occur exclusively between the azides (⁻N=N⁺=N⁻) and alkynes (carbon-carbon triple bond), produce no by-products and therefore have a 100% atom economy. Bioorthogonal ‘Click’ Chemistry has enabled complex chemical reactions to be carried out within living organisms: the reactions do not bring harm to, interfere with or disrupt the biological processes occurring within these systems as they cannot be recognised & used by these systems. ‘Click’ Chemistry is therefore vital in understanding how we may be able to develop Targeted Cancer Therapeutics using Bioorthogonal Chemistry. Modern day cancer treatments tend to be delivered intravenously using anthracyclines (notably doxorubicin), a class of antitumour antibiotics used for cancer chemotherapy: they stop the growth of cancerous cells by preventing their enzymatic machinery from engaging in DNA duplication & cell division, causing the cells to die. The long-standing side effect of using such effective drugs is the high likelihood of ‘off-target toxicity’, where non-cancerous cells can also be harmed by the intercalating effects of the anthracyclines. Frequent targets for this ‘off-target toxicity’ tend to be fast growing body cells, like hair & nails, hence why most cancer patients experience some form of hair loss over the course of their chemotherapy treatment. So, scientists began to consider: what if there was a way to develop targeted cancer treatments? Treatments that enabled the activation of these powerful cancer drugs - anthracyclines - at the tumour sites, mitigating the harm of ‘off-target toxicity’? This is where Bioorthogonal ‘Click’ Chemistry comes in. ‘ C lick- A ctivated P rotodrugs A gainst C ancer’ (or ‘ CAPAC ’) is a platform developed by American Biotechnology Company Shasqi. Through ‘CAPAC’, Shasqi are pioneering the use of Bioorthogonal ‘Click’ Chemistry to target cancer drugs directly to the tumour site, minimising side effects and potentially improving the therapeutic index. They’ve achieved this through exploiting one of the fastest click reactions: a Diels-Alder cycloaddition between a tetrazine (C2H2N4) and a trans-cyclooctene (TCO) - 2 bioorthogonal molecules. The treatment involves two key components: a tetrazine-modified sodium hyaluronate biopolymer & doxorubicin that is connected to a TCO (trans-cyclooctene) unit. Over the course of the treatment (Fig. 2) , the patient will undergo multiple stages: ● Local hydrogel injection: The tetrazine-modified sodium hyaluron ate biopolymer is injected into a patient’s tumour ● Protodrug dose: The patient then receives five daily infusions of doxorubicin-TCO ● Concentration: The drug circulates through the body until it meets the tetrazine-modified biopolymer at the tumour site ● Activation: At the point of meeting, the click reaction brings the tetrazine and TCO together, triggering a rearrangement that frees the doxorubicin right next to the tumour cells Compared to prior cancer treatments, this process would not only mitigate the harm of the drug’s ‘off-target toxicity’, limiting the side-effects of the chemotherapy drug, it would also increase the local concentration of doxorubicin far beyond what would normally be possible in a patient, having a greater effect in preventing the growth of cancer cells. In the treatment of this life-threatening disease, Shasqi’s research into the ‘CAPAC’ platform, though still ongoing, looks excitingly promising: as recently as March 2023, they’ve proven their platform’s efficacy in humans. During a Phase 1 dose-escalation clinical trial in adult patients with advanced solid tumours, Shasqi were able to demonstrate the activation of their tetrazine-modified sodium hyaluronate biopolymer & doxorubicin-TCO at tumour sites, evidencing it’s safety, systemic pharmacokinetics, and immunological activity. With the continuation of their innovative research, the future treatment of cancer can be significantly aided with the use of Bioorthogonal ‘Click’ Chemistry. Written by Emmanuella Fernandez REFERENCES Acs.org . (2021). Click chemistry sees first use in humans . [online] Available at: https://cen.acs.org/pharmaceuticals/Click-chemistry-sees-first-use/98/web/2020/10 . Cancer Research UK (2023). Doxorubicin (Adriamycin) | Cancer drugs | Cancer Research UK . [online] www.cancerresearchuk.org . Available at: https://www.cancerresearchuk.org/about-cancer/treatment/drugs/doxorubicin . Wang, Y., Zhang, C., Wu, H. and Feng, P. (2020). Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs. Molecules , 25(23), p.5640. doi: https://doi.org/10.3390/molecules25235640 . Wikipedia Contributors (2019). Reverse transcriptase . [online] Wikipedia. Available at: https://en.wikipedia.org/wiki/Reverse_transcriptase . Wikipedia. (2020). Zidovudine . [online] Available at: https://en.wikipedia.org/wiki/Zidovudine . Wikipedia. (2022). Bioorthogonal chemistry . [online] Available at: https://en.wikipedia.org/wiki/Bioorthogonal_chemistry . Project Gallery

Looking at the option of nuclear fusion to generate renewable energy Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unleashing the power of the stars: how nuclear fusion holds the key to tackling climate change 14/07/25, 15:08 Last updated: Published: 30/04/23, 10:55 Looking at the option of nuclear fusion to generate renewable energy Imagine a world where we have access to a virtually limitless and clean source of energy, one that doesn't emit harmful greenhouse gases or produce dangerous radioactive waste. A world where our energy needs are met without contributing to climate change. This may sound like science fiction, but it could become a reality through the power of nuclear fusion. Nuclear fusion, often referred to as the "holy grail" of energy production, is the process of merging light atomic nuclei to form a heavier nucleus, releasing an incredible amount of energy in the process. It's the same process that powers the stars, including our very own sun, and holds the potential to revolutionize the way we produce and use energy here on Earth. Nuclear fusion occurs at high temperature and pressure when two atoms (e.g. Tritium and Deuterium atoms) merge together to form Helium. This merge releases excess energy and a neutron. This energy an then be harvested inform of heat to produce electricity. Progress in the field of creating a nuclear fusion reactor has been slow, despites the challenges there are some promising technologies and approaches have been developed. Some of the notable approaches to nuclear fusion research include: 1. Magnetic Confinement Fusion (MCF) : In MCF, high temperatures and pressures are used to confine and heat the plasma, which is the hot, ionized gas where nuclear fusion occurs. One of the most promising MCF devices is the tokamak, a donut-shaped device that uses strong magnetic fields to confine the plasma. The International Thermonuclear Experimental Reactor (ITER), currently under construction in France, is a large-scale tokamak project that aims to demonstrate the scientific and technical feasibility of nuclear fusion as a viable energy source. 2. Inertial Confinement Fusion (ICF) : In ICF, high-energy lasers or particle beams are used to compress and heat a small pellet of fuel, causing it to undergo nuclear fusion. This approach is being pursued in facilities such as the National Ignition Facility (NIF) in the United States, which has made significant progress in achieving fusion ignition, although it is still facing challenges in achieving net energy gain. In December of 2022, the US lab reported that for the first time, more energy was released compared to the input energy. 3. Compact Fusion Reactors: There are also efforts to develop compact fusion reactors, which are smaller and potentially more practical for commercial energy production. These include technologies such as the spherical tokamak and the compact fusion neutron source, which aim to achieve high energy gain in a smaller and more manageable device. While nuclear fusion holds immense promise as a clean and sustainable energy source, there are still significant challenges that need to be overcome before it becomes a practical reality. In nature nuclear fusion is observed in stars, to be able to achieve fusion on Earth such conditions have to be met which can be an immense challenge. High level of temperature and pressure is required to overcome the fundamental forces in atoms to fuse them together. Not only that, but to be able to actually use the energy it has to be sustained and currently more energy is required then the output energy. Lastly, the material and technology also pose challenges in development of nuclear fusion. With high temperature and high energy particles, the inside of a nuclear fusion reactor is a harsh environment and along with the development of sustained nuclear fusion, development of materials and technology that can withstand such harsh conditions is also needed. Despite many challenges, nuclear fusion has the potential to be a game changer in fight against not only climate change but also access of cheap and clean energy globally. Unlike many forms of energy used today, fusion energy does not emit any greenhouse gasses and compared to nuclear fission is stable and does not produce radioactive waste. Furthermore, the fuel for fusion, which is deuterium is present in abundance in the ocean, where as tritium may require to synthesised at the beginning, but once the fusion starts it produce tritium by itself making it self-sustained. When the challenges are weighted against the benefits of nuclear fusion along with the new opportunities it would unlock economically and in scientific research, it is clear that the path to a more successful and clean future lies within the development of nuclear fusion. While there are many obstacles to overcome, the progress made in recent years in fusion research and development is promising. The construction of ITER project, along with first recordings of a higher energy outputs from US NIF programs, nuclear fusion can become a possibility in a not too distant future. In conclusion, nuclear fusion holds the key to address the global challenge of climate change. It offers a clean, safe, and sustainable energy source that has the potential to revolutionize our energy systems and reduce our dependence on fossil fuels. With continued research, development, and investment, nuclear fusion could become a reality and help us build a more sustainable and resilient future for our planet. It's time to unlock the power of the stars and harness the incredible potential of nuclear fusion in the fight against climate change. Written by Zari Syed Related articles: Nuclear medicine / Geoengineering / The silent protectors / Hydrogen cars Project Gallery

The researchers counted over 100,000 neurons and over a billion connections between them within this small cube of brain tissue. To find all the neurons and reconstruct the neural network, researchers had to slice the mouse brain 25,000 times. The issue is Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can a human brain be linked to a computer? Last updated: 06/11/24 Published: 28/12/22 Scientists in the US have succeeded in mapping the three-dimensional structure of the network of neurons in one cubic millimetre of mouse brain- a feat that would require two petabytes of storage. The human brain contains approximately 100 billion neurons, which is one million times the number of neurons found in a cubic millimetre of mouse brain. The researchers counted over 100,000 neurons and over a billion connections between them within this small cube of brain tissue. To find all the neurons and reconstruct the neural network, researchers had to slice the mouse brain 25,000 times. The issue is that the amount of data to store would kill any single computer. Memory and experiences that would have defined people later would be lost if they tried to store their minds too early. Using a computer too late may result in the accumulation of a mind with dementia, which would not work so well. Human tissue would have to be cut into zillions of thin slices using techniques compatible with dying and cutting. Local electrical changes that travel down dendrites and axons allow neurons to communicate with one another. However, when reconstructing the 3D structure, this may not be possible. After we die, our brains undergo significant chemical and anatomical changes. At the age of 20, they begin to lose 85,000 neurons per day due to apoptosis, or programmed cell death. Many memories that would have shaped a person later would be lost if he or she tried to store their mind too early. There are numerous steps involved in developing a computer capable of storing and processing human-level intelligence. It may be impossible for an artificial intelligence to produce sensations and actions identical to those provided and produced by your biological body. Bots are susceptible to hacking and hardware failure. Connecting sensors to the AI's digital mind would also be difficult. Written by Jeevana Thavarajah Related articles: The evolution of AI / Brain metastasis / AI in genetic diagnoses

DFNB9 affects 1 to 16 newborns every 50,000 Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link DFNB9: The first deafness ever treated by gene therapy 09/07/25, 14:02 Last updated: Published: 05/09/24, 10:03 DFNB9 affects 1 to 16 newborns every 50,000 Two (TWO!) AAV gene therapies have restored hearing in deaf patients! Scientists have corrected DFNB9 deafness! These are headlines you have likely read last January. The technology making this achievement possible rightfully took the spotlight (e ven I chimed in! ). But what is DFNB9 deafness in the first place? Why do DFNB9 patients lose their hearing? In a nutshell, DFNB9 deafness is the failure of the ear to share what it has heard with the brain because of mutations in the OTOF gene. Do you want to learn more? Let me explain. Medical and genetic definitions of DFNB9 deafness DFNB9 is a type of genetic deafness. It affects 1 to 16 newborns every 50,000, and it accounts for 2 to 8% of all cases of genetic deafness. DFNB9 is (take a deep breath!) an autosomal recessive prelingual severe-to-profound non-syndromic sensorineural hearing loss. That’s a mouthful of a definition, I agree. Let’s break it down. In medical terms, DFNB9 deafness is: severe — sounds must be louder than 70 dB (think of a vacuum cleaner) to be heard — to profound — sounds must be even louder, over 90 dB (picture a lawn mower), prelingual, that is hearing is lost before developing language skills (2–3 years of age) not associated with other pathologies (non-syndromic). Geneticists describe DFNB9 as an autosomal recessive disease: the gene mutated is not on the sex chromosomes (but on the autosomes) and both alleles must be mutated for the disease to appear (recessive). This gene is OTOF . OTOF encodes otoferlin, a protein that enables the cells detecting sounds to communicate with neurons. As mutations in OTOF disrupt this dialogue, DFNB9 is classified as a sensorineural type of deafness. Otoferlin enables inner hair cells to speak to neurons How does otoferlin enable us to hear? This question needs a few notions on the two main cell types involved in hearing: auditory hair cells and primary auditory neurons. Auditory hair cells are the sound detector. These cells are surmounted by a structure resembling a tuft of hair, the hair bundle. Sounds bend the hair bundle, opening its ion channels; positive ions rush into the cells generating electrical signals that travel across the cell. Inner hair cells — one of the two types of auditory cells — transmit these signals to the primary auditory neurons ( Figure 1 ) The primary auditory neurons are the first station of the nervous pathway between the ear and the brain. Some primary auditory neurons (type I) extend their dendrites to the inner hair cells and listen. The information received is analysed and sent to the brain along the auditory nerve ( Figure 2 ). The synapse is where inner hair cells speak to primary auditory neurons. Otoferlin is essential for this dialogue: without it, inner hair cells cannot share what they have heard. Otoferlin, the calcium sensor At the synapse, synaptic vesicles are placed just beneath the membrane, like Formula 1 cars lined up the grid waiting for the race to start. In response to a sound, electrical signals trigger the opening of calcium channels and calcium ions (Ca2+) rush in. The sudden increase in Ca2+ is the biological equivalent of the “lights out” signal in Formula 1: as soon as Ca2+ enters, the synaptic vesicles rapidly fuse with the membrane. This event releases glutamate onto the primary auditory neurons ( Figure 3 ). The information in the sound is on its way to the brain. In the inner hair cells, otoferlin enables synaptic vesicles to sense changes in Ca2+. Anchored to the vesicles by its tail, otoferlin extends into the cell multiple regions with high affinity to Ca2+ (C2 domains) ( Figure 4 ). The many roles of otoferlin at the synapse Otoferlin is essential throughout the lifecycle of synaptic vesicles (Figure 5). This is a brief overview of its main roles at the synapse: 1 — Docking : Otoferlin helps position vesicles filled with glutamate at the synapse 2 — Priming : Otoferlin interacts with SNARE proteins, which are essential for the fusion with the membrane, and the vesicles become ready to rapidly fuse 3 — Fusion : electrical signals, triggered by sounds, open Ca2+ channels; Otoferlin senses the increase in Ca2+ and prompts the vesicles to fuse with the cell membrane, releasing glutamate 4 — Recycling : Otoferlin helps clear fused vesicles and recycle their components Imperfect knowledge can be enough knowlege (sometimes) Despite years of studies, the functions of otoferlin at the inner hair cell synapse are still elusive. Even more puzzling is the synapse of inner hair cells as a whole. Researchers are captivated and baffled by its mysterious architecture and properties (we would need a new article just to scratch the surface of this topic!). But let’s not forget that we now have two gene therapies to improve the deafness caused by mutations in the OTOF gene. These breakthroughs should encourage us: even with imperfect knowledge, we can (at least in some cases) still develop impactful treatments for diseases. Written by Matteo Cortese, PhD REFERENCES Manchanda A, Bonventre JA, Bugel SM, Chatterjee P, Tanguay R, Johnson CP. Truncation of the otoferlin transmembrane domain alters the development of hair cells and reduces membrane docking. Mol Biol Cell. 2021 Jul 1;32(14):1293–1305. Morton CC, Nance WE. Newborn hearing screening — a silent revolution. N Engl J Med. 2006 May 18;354(20):2151–64. Johnson CP, Chapman ER. Otoferlin is a calcium sensor that directly regulates SNARE-mediated membrane fusion. J Cell Biol. 2010 Oct 4;191(1):187–97. Pangrsic T, Lasarow L, Reuter K, Takago H, Schwander M, Riedel D, Frank T, Tarantino LM, Bailey JS, Strenzke N, Brose N, Müller U, Reisinger E, Moser T. Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nat Neurosci. 2010 Jul;13(7):869–76. Qi J, Tan F, Zhang L, Lu L, Zhang S, Zhai Y, Lu Y, Qian X, Dong W, Zhou Y, Zhang Z, Yang X, Jiang L, Yu C, Liu J, Chen T, Wu L, Tan C, Sun S, Song H, Shu Y, Xu L, Gao X, Li H, Chai R. AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness. Adv Sci (Weinh). 2024 Jan 8:e2306788. Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A, Perfettini I, Le Gall M, Rostaing P, Hamard G, Triller A, Avan P, Moser T, Petit C. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006 Oct 20;127(2):277–89 Vona B, Rad A, Reisinger E. The Many Faces of DFNB9: Relating OTOF Variants to Hearing Impairment. Genes (Basel). 2020 Nov 26;11(12):1411. Project Gallery

Known as microbial endocrinology, it is a complex field Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Investigating the interplay of hormones and the microbiome 10/07/25, 10:19 Last updated: Published: 08/11/24, 12:00 Known as microbial endocrinology, it is a complex field The microbiome The human body hosts a vast ecosystem of bacteria, with trillions crawling on our skin, colonising our gut, and living throughout our bodies. Most of these microbes serve to protect us against infections influencing our metabolism and even our behaviour. However, scientists have started to question the mechanisms by which these bacteria affect our bodily functions and characteristics. Scientists have studied these communities of microorganisms residing within our bodies and the genes they contain, yielding new and exciting perspectives… …Welcome to the human microbiome. The microbiome is the dynamic community of microorganisms (like fungi, bacteria and viruses) that exist in a particular environment. In humans, the term is most often used to describe the collection of microorganisms that inhabit a particular body area, such as the gastrointestinal tract, mouth or skin. While a person’s core microbiome is established within the first few years of life, its composition can shift over time in response to factors like medication, such as potent antibiotics and environmental factors. Researchers have uncovered that the gastrointestinal microbiota can influence some physiological processes, including a direct line of communication between the gut and the brain. But what facilitates this dialogue? What mechanisms enable the gut to relay signals to the brain? The answer is hormones. Hormones and the endocrine system The endocrine system is a network of glands that produce and release chemical messengers known as hormones. They travel via the bloodstream and bind to specific receptors on their target tissues. This binding of hormones to their receptors triggers a response in the target tissue. For instance, during stressful situations, epinephrine (also known as adrenaline) is produced by the adrenal medulla, the inner region of the adrenal glands. This hormone, released into the bloodstream, acts on target tissues such as the heart, where it increases heart rate. Hormones regulate most of the body’s vital functions through their release. Some of these crucial processes include growth, metabolism, and reproduction. In the following sections, however, we specifically focus on how hormones influence the microbiome. The interactions between hormones and the microbiome Exploring the relationship between hormones and the microbiome is known as microbial endocrinology; it is a complex field because there are numerous interactions to account for, and the effects of each one can have lasting impacts on human physiology. For example, epinephrine and norepinephrine can lead to more bacteria, notably E. coli and Pseudomonas aeruginosa , signifying that imbalance could harm humans. Also, parts of the host, ranging from mood to gender, impact hormones, bacterial presence and activity ( Figure 3 ). An emerging area of microbial endocrinology is how the microbiome and sex hormones engage with each other in disease and female health. One paper noted that disorders from metabolic syndrome (MetS) to type 2 diabetes (T2D) have distinctions in the levels of sex hormones and gut microbiota, indicating that they are essential to understanding in developing those conditions. The influence of gut microbiota on sex hormones can occur through various mechanisms, such as bacteria controlling the activity and expression of endocrine receptors and even bacteria metabolising sex hormones; this knowledge can help create treatments against polycystic ovarian syndrome and ovarian cancer, among other diseases that usually impact females due to gut microbiome imbalances ( Figure 4 ). Another part of microbial endocrinology being researched is how the microbiome impacts human growth. In one study involving adult male mice, decreased growth hormone (GH) led to undeveloped microbiomes, while surplus GH was linked to an expanded microbiome; this depicts that bacteria influences development via the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis; maintaining a steady dynamic between the microbiome and this axis is vital for development ( Figure 5 ), particularly in children. In puberty, hormones and the gut microbiome interact, as observed in obesity and precocious puberty. Hence, a deeper awareness of the bacteria and sex hormones during puberty is crucial to designing targeted medicines for growth disorders. Moreover, patients with GH-secreting pituitary adenoma (GHPA) have modified gut microbiota, like increased Alistipes shahii and Odoribacter splanchnicus . Still, more research is needed to investigate this. Conclusion The microbiome refers to the millions of microorganisms on and within the human body that influence various physiological functions ranging from digesting food to outcompeting pathogens for resources. Also, the microbiome can affect the endocrine system, which consists of hormones that control glucose and reproduction, among other processes. This bridge, known as microbial endocrinology, has critical applications for understanding women’s health and growth disorders; this emerging area is growing, so it can address knowledge gaps in diseases like cancer and even improve other medical treatments. Written by Sam Jarada and Fozia Hassan The interactions between hormones and the microbiome, and Conclusion sections by Sam The microbiome, and Hormones and the endocrine system sections by Fozia Related articles: The gut microbiome / Dopamine and the gut / The power of probiotics / Vitamins REFERENCES “The Human Microbiome and Its Impacts on Health - PWOnlyIAS.” PWOnlyIAS , 18 Jan. 2024, pwonlyias.com/current-affairs/gut-microbiome-and-health/ . Accessed 17 Oct. 2024. Mittal, Rahul, et al. “Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.” Journal of Cellular Physiology , vol. 232, no. 9, 10 Apr. 2017, pp. 2359–2372, www.ncbi.nlm.nih.gov/pmc/articles/PMC5772764/ , https://doi.org/10.1002/jcp.25518 . Accessed 17 Oct. 2024. Neuman, Hadar, et al. “Microbial Endocrinology: The Interplay between the Microbiota and the Endocrine System.” FEMS Microbiology Reviews , vol. 39, no. 4, 1 July 2015, pp. 509–521, academic.oup.com/femsre/article/39/4/509/2467625 , https://doi.org/10.1093/femsre/fuu010 . Hiller-Sturmhöfel S, Bartke A. The Endocrine System: An Overview. Alcohol Health and Research World. 2024;22(3):153. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6761896/ Neuman H, Debelius JW, Knight R, Koren O. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiology Reviews [Internet]. 2015 Feb 19 [cited 2024 Sep 18];39(4):509–21. Available from: https://academic.oup.com/femsre/article/39/4/509/2467625?login=false Jose Antonio Santos-Marcos, Mora-Ortiz M, Tena-Sempere M, José López-Miranda, Camargo A. Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases. Biology of Sex Differences. 2023 Feb 7;14(1). He S, Li H, Yu Z, Zhang F, Liang S, Liu H, et al. The Gut Microbiome and Sex Hormone-Related Diseases. Frontiers in Microbiology. 2021 Sep 28;12. Siddiqui R, Makhlouf Z, Alharbi AM, Alfahemi H, Khan NA. The Gut Microbiome and Female Health. Biology [Internet]. 2022 Nov 1;11(11):1683. Available from: https://www.mdpi.com/2079-7737/11/11/1683 Jensen E, Young JA, Jackson Z, Busken J, List EO, Ronan O’Carroll, et al. Growth Hormone Deficiency and Excess Alter the Gut Microbiome in Adult Male Mice. Endocrinology [Internet]. 2020 Feb 26 [cited 2023 Nov 9];161(4). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341558/ Jensen EA, Young JA, Mathes SC, List EO, Carroll RK, Kuhn J, et al. Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: A new frontier for microbial endocrinology. Growth Hormone & IGF Research. 2020 Aug;53-54:101333. Project Gallery

To begin, there was the Humoral Theory, which looked at how disease was caused by gaps in fluids/humours which were: blood, yellow bile, black bile and phlegm, which equated to the elements of air, fire, earth and water respectively. The imbalance can come from habits like overeating Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Key historical events and theories in public health Last updated: 17/11/24 Published: 10/02/23 Introduction Now more than ever, public health has become crucial, which looks at promoting health and preventing disease within a society. There have been numerous events and concepts that have helped shape our current health systems today because without them, it is possible that our health systems would not have advanced without previous knowledge to evolve from. This article will focus on certain key events and concepts. Humoral Theory (Ancient Greek and Roman times) To begin, there was the Humoral Theory, which looked at how disease was caused by gaps in fluids/humours which were: blood, yellow bile, black bile and phlegm, which equated to the elements of air, fire, earth and water respectively. The imbalance can come from habits like overeating and too little/much exercise or external factors such as the weather. This theory was thought to have originated from the Hippocratic Corpus, a compilation of 60 medical documents written during the Ancient Greek era by Hippocrates. Although this theory as we know now is flawed, it did provide a foundational understanding of the human body and was utilised in public health for centuries before being subsequently discredited for the Germ Theory established during the mid-19th century. Miasma Theory (Ancient Greek era to the 19th century) Another theory replaced by Germ Theory was the Miasma theory, which stated that diseases like the plague and cholera were spread due to toxic vapours from the ground/decomposing matter. This theory along with the Humoral theory was accepted for thousands of years since the Ancient Greek era. With regards to the cholera outbreaks in the Victorian era, John Snow’s theory of polluted water causing cholera was initially not accepted by the scientific community during his death in 1858. Eventually though, his theory became accepted when Joseph Bazalgette worked to fix London’s sewage to prevent more deaths by cholera. This event with the Germ Theory led to Miasma and Humoral theories to be disproved, although they provided foundational understanding of how diseases spread. The discovery of vaccines (late 18th century) Aside from theories such as the four humors from above, there were concepts or discoveries that advanced public health measures such as vaccination, which eradicated smallpox and is still used today to prevent the severity of diseases such as COVID-19, influenza and polio. The origins of successful vaccines could be traced back to Edward Jenner who in 1796, retrieved samples from cowpox lesions from a milkmaid because he noticed that contracting cowpox protected against smallpox. With this in mind, he inoculated an 8 year old boy and after this, the boy developed mild symptoms, but then became better. Without this event, it is likely that the human population would significantly decrease as there is more vulnerability to infectious diseases and public health systems being weaker or less stable. Image of a COVID-19 injection. Germ Theory (19th century) As for current scientific theories relating to public health, there is the widely accepted Germ Theory by Robert Koch during the 19th century in the 1860s, stating that microorganisms can cause diseases. He established this theory by looking at cow’s blood through a microscope to see that they died from anthrax and observed rod-shaped bacteria with his hypothesis that they caused anthrax. To test this, he infected mice with blood from the cows and the mice also developed anthrax. After these tests, he developed postulates and even though there are limitations to his postulates at the time like not taking into account prions or that certain bacteria do not satisfy the postulates, they are vital to the field of microbiology, in turn making them important to public health. The establishment of modern epidemiology (19th century) Another key concept for public health is epidemiology, which is the study of the factors as well as distribution of chronic and infectious diseases within populations. One of epidemiology’s key figures is John Snow, who explored the cholera epidemics in London 1854, where he discovered that contaminated water from specific water pumps was the source of the outbreaks. Moreover, John Snow’s work on cholera earned him the title of the “father of modern epidemiology” along with his work providing a basic understanding of cholera. Therefore, this event among others has paved the way for health systems to become more robust in controlling outbreaks such as influenza and measles. Conclusion Looking at the key events above, it is evident that each of them has played an essential role in building the public health systems today through the contributions of the scientists. However, public health, like any other science, is constantly evolving and there are still more future advancements to look forward to that can increase health knowledge. Written by Sam Jarada Related articles: Are pandemics becoming less severe? / Rare zoonotic diseases / How bioinformatics helped with COVID-19 vaccines REFERENCES Lagay F. The Legacy of Humoral Medicine. AMA Journal of Ethics. 2002 Jul 1;4(7). Earle R. Humoralism and the colonial body. Earle R, editor. Cambridge University Press. Cambridge: Cambridge University Press; 2012. Halliday S. Death and miasma in Victorian London: an obstinate belief. BMJ. 2001 Dec 22;323(7327):1469–71. Riedel S. Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University Medical Center). 2005 Jan 18;18(1):21. National Research Council (US) Committee to Update Science, Medicine, and Animals. A Theory of Germs. Nih.gov. National Academies Press (US); 2017. Sagar Aryal. Robert Koch and Koch’s Postulates. Microbiology Notes. 2022. Tulchinsky TH. John Snow, Cholera, the Broad Street Pump; Waterborne Diseases Then and Now. National Library of Medicine. Elsevier; 2018. p. 77–99.