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How do they work? Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A concise introduction to Markov chain models 20/03/25, 11:59 Last updated: Published: 09/03/24, 18:16 How do they work? Introduction A Markov chain is a stochastic process that models a system that transitions from one state to another, where the probability of the next state only depends on the current state and not on the previous history. For example, assuming that X 0 is the current state of a system or process, the probability of a state, X 1 , depends only on X 0 which is of course the current state of the system as stated. P ( X 1 ) = f ( P ( X 0 )) It may be hard to think of any real-life processes that follow this behaviour because there is the belief that all events happen in a sequence because of each other. Here are some examples: Games e.g. chess - If your king is in a certain spot on a chess board, there will be a maximum of 4 transition states that can be achieved that all depend on the initial position of chess piece. The parameters for the Markov model will obviously vary depending on your position on the board which is the essence of the Markov process. Genetics - The genetic code of an organism can be modelled as a Markov chain, where each nucleotide (A, C, G, or T) is a state, and the probability of the next nucleotide depends only on the current one. Text generation - Consider the current state as the most recent word. The transition states would be all possible words which could follow on from said word. Next word prediction algorithms can utilize a first-order Markov process to predict the next word in a sentence based on the most recent word. The text generation example is particularly interesting because only considering the previous word when trying to predict the next word sentence would lead to a very random sentence. That is where we can change things up using various mathematical techniques. k-Order Markov Chains (adding more steps) In a first-order Markov chain, we only consider the immediately preceding state to predict the next state. However, in k-order Markov chains, we broaden our perspective. Here’s how it works: Definition: a k-order Markov chain considers the previous states (or steps) when predicting the next state. It’s like looking further back in time to inform our predictions. Example: suppose we’re modelling the weather. In a first-order Markov chain, we’d only look at today’s weather to predict tomorrow’s weather. But in a second-order Markov chain, we’d consider both today’s and yesterday’s weather. Similarly, a third-order Markov chain would involve three days of historical data. By incorporating more context, k-order chains can capture longer-term dependencies and patterns. As k increases, the model becomes more complex, and we need more data to estimate transition probabilities accurately. See diagram below for a definition of higher order Markov chains. Markov chains for Natural Language Processing A Markov chain can generate text by using a dictionary of words as the states, and the frequency of words in a corpus of text as the transition probabilities. Given an input word, such as "How", the Markov chain can generate the next word, such as "to", by sampling from the probability distribution of words that follow "How" in the corpus. Then, the Markov chain can generate the next word, such as "use", by sampling from the probability distribution of words that follow "to" in the corpus. This process can be repeated until a desired length or end of sentence is reached. That is a basic example and for more complex NLP tasks we can employ more complex Markov models such as k-order, variable, n-gram or even hidden Markov models. Limitations of Markov models Markov models for tasks such as text generation will struggle because they are too simplistic to create text that is intelligent and sometimes even coherent. Here are some reasons why: Fixed Transition Probabilities: Markov models assume that transition probabilities are constant throughout. In reality, language is dynamic, and context can change rapidly. Fixed probabilities may not capture these nuances effectively. Local Dependencies: Markov chains have local dependencies, meaning they only consider a limited context (e.g., the previous word). They don’t capture long-range dependencies or global context. Limited Context Window: Markov models have a fixed context window (e.g., first-order, second order, etc.). If the context extends beyond this window, the model won’t capture it. Sparse Data : Markov models rely on observed data (transition frequencies) from the training corpus. If certain word combinations are rare or absent, the model struggles to estimate accurate probabilities. Lack of Learning: Markov models don’t learn from gradients or backpropagation. They’re based solely on observed statistics. Written by Temi Abbass Related articles: Latent space transformation s / Evolution of AI FURTHER READING 1. “Improving the Markov Chain Approach for Generating Text Used for…” : This work focuses on text generation using Markov chains. It highlights the chance based transition process and the representation of temporal patterns determined by probability over sample observations . 2 . “Synthetic Text Generation for Sentiment Analysis” : This paper discusses text generation using latent Dirichlet allocation (LDA) and a text generator based on Markov chain models. It explores approaches for generating synthetic text for sentiment analysis . 3. “A Systematic Review of Hidden Markov Models and Their Applications” : This review paper provides insights into HMMs, a statistical model designed using a Markov process with hidden states. It discusses their applications in various fields, including robotics, finance, social science, and ecological time series data analysis . Project Gallery

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

In some cases, the exact cause of vertigo remains unidentified, highlighting the complexity of diagnosis Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Vertigo Last updated: 27/06/25, 14:06 Published: 03/07/25, 07:00 In some cases, the exact cause of vertigo remains unidentified, highlighting the complexity of diagnosis Vertigo is a symptom characterised by the sensation of spinning or movement, affecting either the individual or their surroundings. Unlike dizziness, which involves a floating sensation, or imbalance, which reflects unsteadiness, vertigo conveys a distinct sense of motion. While it is not a condition in itself, vertigo often indicates an underlying issue and can range from mild to debilitating, significantly impairing balance and daily activities. Physiology of vertigo Physiologically, vertigo is primarily linked to the inner ear and the vestibular system, which is responsible for maintaining balance and spatial orientation. The vestibular apparatus consists of semicircular canals and otolith organs, which detect angular and linear movements, respectively. Dysfunction in these structures, or their neural pathways to the brainstem and cerebellum, can disrupt normal sensory input, causing vertigo. Symptoms ( Figure 1 ) may include a spinning sensation, nausea, vomiting, nystagmus (involuntary eye movements), sweating, and difficulty with balance. Triggers vary widely and may include head movements, changes in position, or even psychological stress. The underlying causes can be peripheral, such as inner ear disorders, or central, involving the brain or central nervous system. Causes and prevalence Vertigo is particularly common among middle-aged and older adults, where it presents a considerable risk of falls and associated injuries. This demographic is especially vulnerable due to age-related changes in the vestibular system, such as a decline in vestibular hair cells and neurons, as well as alterations in central pathways. Vestibular disorders are among the most frequent causes of vertigo episodes in the elderly, often contributing to a cycle of psychological distress and physical limitation. Anxiety and depressive syndromes further exacerbate this cycle by increasing fear of attacks and falls, ultimately limiting daily activities and lowering perceived quality of life. Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of vertigo and is featured in multiple studies within the literature ( Figure 2 ). BPPV is typically triggered by changes in head position, leading to brief episodes of intense vertigo. Despite its prevalence, management can be challenging due to the nonspecific nature of symptoms and the diverse underlying causes. Polypharmacy, or the use of multiple medications, has also emerged as a significant factor in vertigo among older adults. Prescriptions involving several drugs, particularly antihypertensives and sedative hypnotics, have been linked to an increased likelihood of vertigo. Careful assessment of medication interactions and side effects during medical consultations is therefore essential. Metabolic disorders, such as diabetes and hypoglycaemia, also contribute to vertigo in some individuals. However, in a portion of cases, the exact cause of vertigo remains unidentified, highlighting the complexity of diagnosis. Conclusion As one of the most common and disabling symptoms in the elderly, vertigo requires comprehensive and individualised care. Understanding its underlying physiological mechanisms, as well as recognising the multifactorial influences such as medication use, psychological health, and metabolic disorders, is essential for effective management. By adopting an integrated approach that prioritises accurate diagnosis and targeted interventions, clinicians can improve both symptom control and overall quality of life for individuals affected by vertigo. Further research is needed to enhance treatment strategies and address the remaining gaps in knowledge. Written by Maria Z Kahloon Project Gallery

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

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

A Scientia News Biology and Genetics collaboration Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Germline gene therapy (GGT): its potential and problems 09/07/25, 14:14 Last updated: Published: 21/01/24, 11:47 A Scientia News Biology and Genetics collaboration Introduction Genetic diseases arise when there are alterations or mutations to genes or genomes. In most acquired cases, mutations occur in somatic cells. However, when these mutations happen in germline cells (i.e. sperm and egg cells), they are incorporated into the genome of every cell. In other words, should this mutation be deleterious, all cells will have this issue. Furthermore, this mutation becomes inheritable. This is partly why most genetic diseases are complicated to treat and cure. Gene therapy is a concept that has been circulating among geneticists for some time. Indeed, addressing a disease directly from the genes that caused or promoted it has been an attractive and appealing avenue of therapies. The first successful attempt at gene therapy dates back to 1990, using retrovirus-derived vectors to transduce the T-lymphocytes of a 4-year-old girl with X-linked severe combined immunodeficiency disease (SCID-X1) with enzyme adenosine deaminase (ADA) deficiency. The trial was a great success, eliminating the girl's disease and marking a great milestone in the history of genetics. Furthermore, the success of viral vectors also opened new avenues to gene editing, such as zinc finger nucleases and the very prominent CRISPR-Cas9. For example, in mid-November 2023, the UK Medicines and Healthcare products Regulatory Agency or MHRA approved the CRISPR-based gene therapy, Casgevy, for sickle cell disease and β-thalassemia. It is clear that the advent of gene therapies significantly shaped the treatment landscape and our approach to genetic disorders. However, for most of gene therapy history, it is done almost exclusively on somatic cells or some stem cells, not germline cells. How it works As mentioned, inherited genetic disease-associated mutations are also present in germline cells or gametes. The current approach to gene therapy targets genes of some or very specific somatic or multipotent stem cells. For example, in the 1990 trial, the ADA-deficient SCID-X1 T-lymphocytes were targeted, and in recently approved Casgevy, the BCL11A erythroid-specific enhancer in hematopoietic stem cells. The methods involved in gene therapies also vary, each with advantages and limitations and carrying some therapeutic risks. Nevertheless, when aiming to treat genetic diseases, gene therapy should answer two things: how to do it and where. There are a few elucidated strategies of gene therapies. Unlike some popular beliefs, gene therapies do not always directly change or edit mutated genes. Instead, some gene therapies target enhancers or regulatory regions that control the expression of mutated genes. In other cases, such as in Casgevy, enhancers of a different subtype are targeted. By targeting or reducing BCL11A expression, Casgevy aims to induce the production of foetal haemoglobin (HbF), which contains the γ-globin chain as opposed to the defective β-chain in the adult haemoglobin (HbA) of sickle cell disease or β-thalassemia. Some gene therapies can also be done ex vivo or in vivo . Ex vivo strategies involve extracting cells from the body and modifying them in the lab, whilst in vivo strategies directly modify the cell without extraction (e.g. using viral/ non-viral vectors to insert genes). In essence, the list of strategies for gene therapies is growing, each with limitations and a promising prospect of tackling genetic diseases. These methods aim to “cure” genetic diseases in patients. However, the strategies mentioned above have all been researched using and, perhaps, made therapeutically for somatic or multipotent stem cells. Germline gene therapy (GGT), involves directly editing the genetic materials of germline cells or the egg and sperm cells before fertilisation. This means if it is done successfully, fertilisation of these cells will eliminate the disease phenotype from all cells of the offspring instead of only effector cells. Potentially, GGT may eradicate a genetic disease for all future generations. Therefore, it is an appealing alternative to human embryo editing, as it achieves similar or the same result without the need to modify an embryo. However, due to its nature, its advantage may also be its limitation. Ethical issues GGT has the potential to cure genetic disorders within families. However, because it involves editing either the egg or sperm cells before fertilisation, there are prominent ethical issues associated with this method, like the use of embryos for research and many more. Firstly, GGT gives no room for error. Mistakes during the gene modification process could cause systemic side effects or a harsher disease than the one initially targeted, leading to a multigenerational effect. For example, if parents went to a clinic to check if one/both their germ cells have a gene coding for proteins implicated in cystic fibrosis, an off-target mistake during GGT may lead to their child developing Prader-Willi Syndrome or other hereditary disorders caused by editing out significant genes for development. Secondly, an ecological perspective asserts that the current human gene pool, an outcome of many generations of natural selection, could be weakened by germline gene editing. Also, there is the religious perspective, where editing embryos goes against the natural order of how god created living creatures as they should be, where their natural phenotypes are “assigned” for when they are alive. Another reason GGT may be unethical is it leads to eugenics or creating “designer babies”. These are controversial ideas dating back to the late 19th century, where certain traits are “better” than others. This implies they should appear in human populations while individuals without them should be sterilised/killed off. For instance, it is inconceivable to forget the Nazi Aktion T4 program, which sought to murder disabled people because they were seen as “less suitable” for society. Legal and social issues Eugenics is notorious today because of its history. Genetic counselling may be seen like this as one possible outcome may be parents who end pregnancies if their child inherits a genetic disease. Moreover, understanding GGT’s societal influences is crucial, so clinical trial designs must consider privacy, self-ownership, informed consent and social justice. In China, the public’s emotional response to GGT in 2018 was mainly neutral, as shown in Figure 1, but some of the common “hot words” when discussed were ‘mankind’, ‘ethics’, and ‘law’. With this said, regulations are required with other nations for a wider social consensus on GGT research. In other countries, there are stricter rules for GGT. it is harder to conduct experiments using purposely formed/altered human embryos with inheritable mutations in the United States because the legal outcomes can include prison time and $100,000 fines. Furthermore, when donors are required, they must be fairly compensated, and discussing methodologies is crucial because there are issues on how they can impact men and women. South Africa has two opposing thoughts on GGT or gene editing. Bioconservatism has worries about genetic modification and asserts its restrictions, while bioliberalism is receptive to this technology because of the possible benefits. Likewise, revisions to the current regulations are suggested, such as rethinking GGT research or a benefit-risk analysis for the forthcoming human. Conclusion Overall, gene therapies have transformed the therapeutic landscape for genetic diseases. GGT is nevertheless a unique approach that promises to completely cure a genetic disease for families without the need to edit human embryos. However, GGT’s prospects may do more harm than good because its therapeutic effects are translated systemically and multigenerationally. On top of that, controversial ideas such as designer babies can arise if GGT is pushed too far. Additionally, certain countries have varying regulations due to cultural attitudes towards particular scientific innovations and the beginning of life. Reflecting on the ethical, legal and social issues, GGT is still contentious and probably would not be a prominent treatment option anytime soon for genetic diseases. Written by Sam Jarada and Stephanus Steven Introduction, and How it works by Stephanus Ethical issues, and Legal and social issues by Sam Conclusion by Sam and Stephanus Related article: Monkey see, monkey clone References: Cavazzana-Calvo, M. et al. (2000) ‘Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease’, Science , 288(5466), pp. 669–672. doi:10.1126/science.288.5466.669. Demarest, T.G. and Biferi, M.G. (2022) ‘Translation of gene therapy strategies for amyotrophic lateral sclerosis’, Trends in Molecular Medicine , 28(9), pp. 795–796. doi:10.1016/j.molmed.2022.07.001. Frangoul, H. et al. (2021) ‘CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia’, New England Journal of Medicine , 384(3), pp. 252–260. doi:10.1056/nejmoa2031054. AGAR, N. (2018). Why We Should Defend Gene Editing as Eugenics. Cambridge Quarterly of Healthcare Ethics, 28(1), pp.9–19. doi: https://doi.org/10.1017/s0963180118000336 . de Miguel Beriain, I., Payán Ellacuria, E. and Sanz, B. (2023). Germline Gene Editing: The Gender Issues. Cambridge Quarterly of Healthcare Ethics, 32(2), pp.1–7. doi: https://doi.org/10.1017/s0963180122000639 . Genome.gov . (2021). Eugenics: Its Origin and Development (1883 - Present). [online] Available at: https://www.genome.gov/about-genomics/educational-resources/timelines/eugenics#:~:text=Discussions%20of%20eugenics%20began%20in . Johnston, J. (2020). Budgets versus Bans: How U.S. Law Restricts Germline Gene Editing. Hastings Center Report, 50(2), pp.4–5. doi: https://doi.org/10.1002/hast.1094 . Kozaric, A., Mehinovic, L., Stomornjak-Vukadin, M., Kurtovic-Basic, I., Catibusic, F., Kozaric, M., Mesihovic-Dinarevic, S., Hasanhodzic, M. and Glamuzina, D. (2016). Diagnostics of common microdeletion syndromes using fluorescence in situ hybridization: single center experience in a developing country. Bosnian Journal of Basic Medical Sciences, [online] 16(2). doi: https://doi.org/10.17305/bjbms.2016.994 . Luque Bernal, R.M. and Buitrago BejaranoR.J. (2018). Assessoria genética: uma prática que estimula a eugenia? Revista Ciencias de la Salud, 16(1), p.10. doi: https://doi.org/10.12804/revistas.urosario.edu.co/revsalud/a.6475 . Nielsen, T.O. (1997). Human Germline Gene Therapy. McGill Journal of Medicine, 3(2). doi: https://doi.org/10.26443/mjm.v3i2.546 . Niemiec, E. and Howard, H.C. (2020). Germline Genome Editing Research: What Are Gamete Donors (Not) Informed About in Consent Forms? The CRISPR Journal, 3(1), pp.52–63. doi: https://doi.org/10.1089/crispr.2019.0043 . Peng, Y., Lv, J., Ding, L., Gong, X. and Zhou, Q. (2022). Responsible governance of human germline genome editing in China. Biology of Reproduction, 107(1). doi: https://doi.org/10.1093/biolre/ioac114 . Shozi, B. (2020). A critical review of the ethical and legal issues in human germline gene editing: Considering human rights and a call for an African perspective. South African Journal of Bioethics and Law, 13(1), p.62. doi: https://doi.org/10.7196/sajbl.2020.v13i1.00709 . Thaldar, D., Botes, M., Shozi, B., Townsend, B. and Kinderlerer, J. (2020). Human germline editing: Legal-ethical guidelines for South Africa. South African Journal of Science, 116(9/10). doi: https://doi.org/10.17159/sajs.2020/6760 . Zhang, D. and Lie, R.K. (2018). Ethical issues in human germline gene editing: a perspective from China. Monash Bioethics Review, 36(1-4), pp.23–35. doi: https://doi.org/10.1007/s40592-018-0091-0 . Project Gallery

Julius Oppenheimer Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The chemistry of an atomic bomb 04/07/25, 12:57 Last updated: Published: 23/08/23, 16:29 Julius Oppenheimer Julius Robert Oppenheimer, often credited with leading the development of the atomic bomb, played a significant role in its creation in the early 1940s. However, it is essential to recognise the collaborative effort of many scientists, engineers, and researchers who contributed to the project. The history and chemistry of the atomic bomb are indeed fascinating, shedding light on the scientific advancements that made it possible. The destructive power of an atomic bomb stems from the rapid release of energy resulting from the splitting, or fission, of fissile atomic nuclei in its core. Isotopes such as uranium-235 and plutonium-239 are selected for their ability to undergo fission readily and sustain a self-sustaining chain reaction, leading to the release of an immense amount of energy. The critical mass of fissionable material required for detonation ensures that the neutrons produced during fission have a high probability of impacting other nuclei and initiating a chain reaction. To facilitate a controlled release of energy, neutron moderation plays a crucial role in the functioning of an atomic bomb. Neutrons emitted during fission have high velocities, making them less likely to be absorbed by other fissile material. However, by employing a moderator material such as heavy water (deuterium oxide) or graphite, these high-speed neutrons can be slowed down. Slowing down the neutrons increases the likelihood of their absorption by fissile material, enhancing the efficiency of the chain reaction and the release of energy. The sheer magnitude of the energy released by atomic bombs is staggering. For example, one kilogram (2.2 pounds) of uranium-235 can undergo complete fission, producing an amount of energy equivalent to that released by 17,000 tons (17 kilotons) of TNT. This tremendous release of energy underscores the immense destructive potential of atomic weapons. It is essential to note that the development of the atomic bomb represents a confluence of scientific knowledge and technological advancements, with nuclear chemistry serving as a foundational principle. The understanding of nuclear fission, the critical mass requirement, and the implosion design were key factors in the creation of the atomic bomb. Exploring the chemistry behind this devastating weapon not only provides insights into the destructive capabilities of atomic energy but also emphasises the responsibility that accompanies its use. In conclusion, while Oppenheimer's contributions to the development of the atomic bomb are significant, it is crucial to acknowledge the collective effort that led to its creation. The chemistry behind atomic bombs, from the selection of fissile isotopes to neutron moderation, plays a pivotal role in harnessing the destructive power of nuclear fission. Understanding the chemistry of atomic weapons highlights the remarkable scientific achievements and reinforces the need for responsible use of atomic energy. Written by Navnidhi Sharma Project Gallery

The main difference between children and adults lies in what needs to be rebuilt Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Why brain injuries affect children and adults differently Last updated: 12/11/25, 12:09 Published: 13/11/25, 08:00 The main difference between children and adults lies in what needs to be rebuilt When we think about a brain injury, it is easy to assume that the same thing happens in everyone; a bump to the head, swelling, and hopefully a recovery. In reality, things aren’t quite that simple. A child’s brain is not a smaller version of an adult’s, it is still developing, which makes it both incredibly adaptable and, at the same time, especially vulnerable. Smaller bodies, bigger risks Although the brain’s basic reaction to injury is similar in children and adults, injuries in younger people tend to cause more widespread and severe damage. This is due to the differences in anatomical development. Children’s heads are proportionally larger compared to the rest of their bodies, and their neck muscles are much weaker than those of adults. This means that when a child falls or is knocked, their head can move suddenly and forcefully, placing extra strain on the brain. On top of that, children’s brains have a higher water content and are softer in texture, which makes them more vulnerable to rotational forces and acceleration-deceleration injuries. These types of movements can lead to diffuse axonal injury, where nerve fibres are torn across large areas, and cerebral swelling, both of which are less common in adults experiencing similar trauma. A clear example of this vulnerability is seen in abusive head trauma. When an infant is shaken, their softer skull and brain structure can lead to a combination of skull fractures, internal bleeding, and swelling. Sadly, these injuries are often linked to very poor outcomes. The double-edged sword of brain plasticity One of the most remarkable things about the young brain is its plasticity, which is its ability to reorganise itself and form new connections after injury. This flexibility often means that children recover some functions, such as movement or daily activities, more quickly than adults do in the early months after a brain injury. However, this adaptability has limits. During childhood, the brain is constantly developing new skills and abilities. If an injury occurs during one of these critical periods, it can interrupt processes essential for normal development. This means that difficulties might not appear straight away. A child could seem to recover well at first but then struggle later when their brain is expected to handle more complex tasks, such as problem-solving or emotional regulation. Over time, recovery often plateaus, and children may continue to face long-term challenges with learning, behaviour, and social interaction. Research also shows that injury severity is a major factor in long-term outcomes. Children who suffer severe traumatic brain injuries are more likely to experience lower academic performance and, later in life, face higher rates of unemployment or lower paid work compared with their peers. Behaviour, learning and life after injury Brain injuries in childhood can also affect behaviour and mental health. Conditions such as ADHD are especially common following injury, affecting between 20-50% of children. These difficulties can make returning to school and social life far more challenging. Children from lower socioeconomic backgrounds often experience extra barriers, including limited access to rehabilitation and educational support. This can increase the risk of social isolation and mental health difficulties. Children are also more likely than adults to develop secondary brain conditions, such as epilepsy, after an injury which adds further complexity to their recovery. Why recovery is not the same The main difference between children and adults lies in what needs to be rebuilt. Adults are generally trying to re-learn skills they already had, while children are still learning those skills for the first time. That makes recovery a much more delicate and unpredictable process. Moreover, most rehabilitation is concentrated in the first few months after the injury, but children’s challenges often become clearer years later, when their brains, and the demands placed on them, have developed further. In summary The developing brain is both fragile and flexible . While its biological features make it more prone to injury, its capacity for plasticity allows for impressive short-term recovery. Yet the same developmental processes that support growth also make it more vulnerable to long-term disruption. Injuries sustained during childhood can alter the course of brain development, leading to lasting effects on thinking, learning, and behaviour. These consequences can shape a person’s future long after the initial recovery period has ended. Understanding these differences is crucial, not just for doctors, but also for teachers, parents, and anyone supporting a young person recovering from a brain injury. Written by Alice Greenan Related articles: Synaptic plasticity / Traumatic Brain Injury (TBI) / Childhood intelligence REFERENCES Anderson, V. (2005). Functional Plasticity or Vulnerability After Early Brain Injury? PEDIATRICS , 116 (6), 1374–1382. https://doi.org/10.1542/peds.2004-1728 Anderson, V., Brown, S., Newitt, H., & Hoile, H. (2011). Long-term outcome from childhood traumatic brain injury: Intellectual ability, personality, and quality of life. Neuropsychology , 25 (2), 176–184. https://doi.org/10.1037/a0021217 Anderson, V., & Yeates, K. O. (2010). Pediatric Traumatic Brain Injury. In Cambridge University Press eBooks . Cambridge University Press. https://doi.org/10.1017/cbo9780511676383 ARAKI, T., YOKOTA, H., & MORITA, A. (2017). Pediatric Traumatic Brain Injury: Characteristic Features, Diagnosis, and Management. Neurologia Medico-Chirurgica , 57 (2), 82–93. https://doi.org/10.2176/nmc.ra.2016-0191 Blackwell, L. S., & Grell, R. M. (2023). Pediatric Traumatic Brain Injury: Impact on the Developing Brain. Pediatric Neurology . https://doi.org/10.1016/j.pediatrneurol.2023.06.019 Figaji, A. A. (2017). Anatomical and Physiological Differences between Children and Adults Relevant to Traumatic Brain Injury and the Implications for Clinical Assessment and Care. Frontiers in Neurology , 8 (685). https://doi.org/10.3389/fneur.2017.00685 Manfield, J., Oakley, K., Macey, J.-A., & Waugh, M.-C. (2021). Understanding the Five-Year Outcomes of Abusive Head Trauma in Children: A Retrospective Cohort Study. Developmental Neurorehabilitation , 24 (6), 1–7. https://doi.org/10.1080/17518423.2020.1869340 Narad, M. E., Kaizar, E. E., Zhang, N., Taylor, H. G., Yeates, K. O., Kurowski, B. G., & Wade, S. L. (2022). The Impact of Preinjury and Secondary Attention-Deficit/Hyperactivity Disorder on Outcomes After Pediatric Traumatic Brain Injury. Journal of Developmental & Behavioral Pediatrics , 43 (6), e361–e369. https://doi.org/10.1097/dbp.0000000000001067 Neumane, S., Câmara-Costa, H., Francillette, L., Araujo, M., Toure, H., Brugel, D., Laurent-Vannier, A., Ewing-Cobbs, L., Meyer, P., Dellatolas, G., Watier, L., & Chevignard, M. (2021). Functional outcome after severe childhood traumatic brain injury: Results of the TGE prospective longitudinal study. Annals of Physical and Rehabilitation Medicine , 64 (1), 101375. https://doi.org/10.1016/j.rehab.2020.01.008 Parker, K. N., Donovan, M. H., Smith, K., & Noble-Haeusslein, L. J. (2021). Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress. Frontiers in Neurology , 12 . https://doi.org/10.3389/fneur.2021.708800 Project Gallery

How botox works in the cosmetic industry Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link From botulism to beauty: the evolution of botulinum toxins and botox 09/07/25, 14:10 Last updated: Published: 03/10/23, 14:07 How botox works in the cosmetic industry Botulinum neurotoxins (BoNTs) rank amongst the most potent and lethal neurotoxins known to science. Yet, it's a fascinating journey to discover how these deadly substances have found their way into one of the most renowned cosmetic procedures in the world: Botox. BoNTs originate from the bacterium Clostridium botulinum , which produces some of the most potent neurotoxins in existence. They are central to the development of botulism, a condition that relentlessly targets the body's nervous system, resulting in challenges in breathing and muscle paralysis. Despite their perilous origins, these toxins have undergone a fascinating metamorphosis into a popular cosmetic procedure. They have been studied substantially due to their ability to block nerve functions leading to muscle paralysis and their unique pharmacological properties in therapeutic and cosmetic uses. They affect the neurotransmission process by blocking the release of acetylcholine that allows muscle contraction in the body. The toxins bind pre-synaptically to recognition sites on cholinergic nerve terminals resulting in the inhibition of neurotransmitter release. The toxin consists of a heavy chain and a light chain connected by a disulphide bond. This disulphide bond is vital in the entry of the metalloprotease chain in the cytosol. BoNTs have a unique binding characteristic as a dual receptor binder, which allows them to achieve a high affinity for neurons. These proteins possess the remarkable ability to specifically target and interfere with the neurotransmission process. At their core, BoNTs are proteases, enzymes specialised in cleaving specific proteins involved in nerve signal transmission. When administered as Botox, BoNTs are skillfully harnessed to their advantage due to these properties. By injecting small, controlled amounts into specific facial muscles, they temporarily disrupt the nerve signals that stimulate muscle contraction. This action leads to muscle relaxation, smoothing out wrinkles and lines on the skin's surface. Importantly, the effects are localised, preserving the natural expressiveness of the face. In 1989, BoNTs made their debut in the medical community by being recognised as a safe and effective treatment by the FDA for blepharospasm, which affects eye muscle control. However, in 2002 the FDA extended its endorsement, propelling Botox into the realm of beauty. This pivotal decision forever reshaped the landscape of cosmetic procedures, solidifying Botox's status as an iconic treatment for rejuvenation and enhancement. In conclusion, the evolution of botulinum toxins and the rise of Botox is a captivating journey that traverses the realms of science, medicine, and evolving beauty ideals. Written by Anam Ahmed Project Gallery

The same condition after all? Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder 09/07/25, 14:21 Last updated: Published: 20/01/24, 11:38 The same condition after all? Practice and progress in rheumatology The relationship between hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD) has been hotly debated in recent years, with research being published on a near-constant basis attempting to establish a valid symptomatological or causalogical difference between the two disorders. Now, a paper by Ritelli et al. (2022) threatens to end the savage cycle for all. Using RNA sequencing techniques and immunofluorescence, Ritelli et al. found identical gene expression and cellular characteristics in dermal biopsies from those with both conditions. Through immunofluorescence of biopsies from 20 women with hEDS, 16 women and 4 men with HSD and 40 controls, it was found that the shape and components of the extracellular matrix were greatly different in those with HSD/hEDS in comparison to those in the healthy control group. Abnormalities were discovered in the expression of cadherin-11, snail1, and αvβ3, α5β1 and α2β1 integrins. Integrins mediate the connections between the cell cytoskeleton and extracellular matrix to ensure they stay together, cell-to-cell adhesion is initiated by cadherin-11, and snail1 is localised close to the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene. Snail1 can activate CDKN2B gene products when Snail1 is overexpressed to the point of reaching the general localisation of the CDKN2B domain. This demonstrates that there may be a similar causative link between the widespread inflammation and chronic pain in HSD/hEDS and rheumatoid arthritis. Li et al. (2021) proved that the polarisation of macrophages (white blood cells which destroy foreign products) was carefully controlled by the CDKN2B-AS1/ MIR497/TXNIP axis- the increased activation of which in rheumatoid arthritis catalyses the excessive polarisation of macrophages, which causes the macrophages to attack healthy cells. In rat studies published by Tan et al. (2022), it was found that rats with diabetes and induced sepsis experienced greater intestinal injury that control rats without any medical pathology who experienced induced sepsis. This was demonstrated to be due to interruptions in the miR-3061/Snail1 communication pathway. Research on this phenomenon in humans may elucidate the relevance of snail1 overproduction in hEDS/HSD sufferers to their complex gastrointestinal symptoms. If this pathway works similarly in human models of sepsis or localised GI infection, it may intimate that snail1 overproduction is responsible for the hyperpolarisation of macrophages in response to foreign product detection, which may cause immunological damage in the intestines. However, the relevance of this study to hEDS/HSD should be considered questionable until further human research into this avenue has been completed. The result of this research is that academia can potentially derive a genetic cause of the complex phenotypes demonstrated by sufferers of hEDS/HSD. This can be achieved by visualising the human genome, and testing genes like those above, or those implicated in modulating the activity of the genes above. Once garnered, this genetic evidence will elucidate whether or not hEDS and HSD are one disorder, or both variants of the same disorder with differing genetic causes. This, in turn, could lead to the development of medications or treatments based on genetic phenotype. Written by Aimee Wilson Related articles: Ehlers-Danlos syndrome / Types of movement Project Gallery