The Science Behind ‘Hanger’ At its core, hanger stems from the brain’s complex response to a drop in blood sugar levels. Glucose is the brain’s primary source of energy, and when we go too long without food, glucose levels dip. This triggers a cascade of events within the hypothalamus—a key brain region responsible for regulating hunger and emotions. When the hypothalamus detects low blood sugar, it sends signals to other parts of the brain, including the limbic system, which governs emotional responses. Suddenly, emotions become harder to control. This is where the “hanger” phenomenon kicks in: the brain shifts its focus from higher-order functions like patience and rational thinking to more primal instincts—seeking food as quickly as possible. Neuropeptides and Aggression Key players in this emotional response are neuropeptides like NPY (Neuropeptide Y), which increase in response to hunger. NPY has been linked to aggressive behavior, particularly when the body perceives a threat to survival. When glucose levels are low, the body interprets this as a potential danger, triggering an aggressive drive to find sustenance. Research published in the journal Nature found that animals with higher NPY levels exhibited more aggressive behaviors when hungry. While this aggression is useful in the wild for survival, in modern society, it translates into irritability and short tempers. Stress, Cortisol, and Blood Sugar Adding to the mix is cortisol, the hormone released in response to stress. Hunger itself is a stressor, leading to an increase in cortisol levels, which in turn exacerbates feelings of frustration and anger. A study from the University of Guelph found that people who experienced prolonged periods of low blood sugar also had elevated cortisol levels, directly linking stress and hunger. Why Do Some People Get Hangrier Than Others? Not everyone experiences hanger to the same degree, and researchers suggest this may be due to individual differences in how the brain processes hunger signals. Genetic variations in the production of certain neuropeptides, as well as differences in stress hormone regulation, may play a role. People who are more sensitive to changes in blood sugar levels or who have a higher baseline level of stress may be more prone to experiencing hanger. Moreover, psychological factors such as mood regulation and emotional resilience can impact how one handles hunger. Some people have trained their brains to better tolerate discomfort, while others might feel immediate frustration when hunger strikes. Managing Hanger: A Brain-Based Approach Understanding the neuroscience behind hanger can help us manage it better. To keep blood sugar levels stable, eating regular, balanced meals that include proteins, fats, and carbohydrates is crucial. Additionally, stress-management techniques like mindfulness and deep breathing can help mitigate the emotional surge that accompanies hunger. For those who struggle with hanger frequently, small snacks like nuts or fruits between meals can prevent the blood sugar dips that trigger this emotional reaction. A Complex Emotional Cocktail The next time you feel the familiar pangs of hunger morphing into irritation, remember that it’s not just in your head—it’s in your neurons. The intricate dance between blood sugar levels, neuropeptides, and stress hormones creates the perfect storm for hanger, reminding us that even our most basic needs can have a profound impact on our emotional well-being. Our brains are wired to protect us, but knowing how these systems work can help us avoid being at the mercy of hunger’s emotional toll. So, stay fueled, stay balanced, and perhaps avoid that next potential hanger episode. References: 1. Blouet, Chloe, and Denis Burdakov. "Hypothalamic Control of Glucose Homeostasis: The Role of Glucose-Sensing Neurons." Endocrinology, vol. 160, no. 6, 2019, pp. 1411–1420. Oxford Academic 2. Qi, Y., et al. "Agrp-negative Arcuate NPY Neurons Drive Feeding under Positive Energy Balance." Cell Metabolism, vol. 28, no. 6, 2018, pp. 1031-1040. Cell 3. Nakamura, Y., et al. "Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic and Feeding Responses." Cell Metabolism, vol. 29, no. 5, 2019, pp. 1259-1272. Cell.

The Frontline Defense of Nasal Immunity The nasal cavity is the first point of contact for airborne pathogens, including viruses, bacteria, and allergens. To combat these invaders, the nose is equipped with an army of immune cells, such as neutrophils and macrophages, which are on constant patrol. These cells work in concert with mucus and cilia (tiny hair-like structures) to trap, neutralize, and expel harmful particles. This immune response in the nose is more than just a barrier—it is a dynamic and highly specialized defense mechanism. The recent study in Nature highlights how these immune cells can effectively identify and respond to pathogens at the moment of entry, providing a rapid response that prevents infections from spreading further into the respiratory system. Implications for Respiratory Health and Vaccines The discovery of the nose’s immune capabilities has significant implications for public health, particularly in the context of respiratory diseases like COVID-19. Traditional vaccines administered via injection often focus on systemic immunity, which operates throughout the body. However, understanding and enhancing nasal immunity could lead to more effective strategies for preventing respiratory infections. For example, nasal spray vaccines could be developed to stimulate these local immune cells directly, offering targeted protection where it’s most needed. This approach could complement existing vaccines and provide an additional layer of defense, particularly against respiratory viruses that enter through the nose. Nasal Immunity and Allergic Reactions Interestingly, the nose’s immune system is also involved in regulating responses to allergens. When it functions properly, it can distinguish between harmful pathogens and benign substances like pollen or dust. However, in some cases, this system can overreact, leading to allergic rhinitis, commonly known as hay fever. Understanding how to modulate this immune response could lead to better treatments for allergies. The Future of Nasal Immune Research The research highlighted in Nature is just the beginning. As scientists continue to explore the intricacies of nasal immunity, we can expect to see new therapies and preventive measures that harness this powerful defense system. From improving vaccine delivery to developing novel treatments for respiratory diseases, the potential applications are vast and promising. In conclusion, the nose is not just a passive passage for air—it’s an active and crucial player in our immune defense. As we learn more about how nasal immune cells work, we’re uncovering new ways to protect ourselves from the myriad of pathogens that we encounter every day. References: 1. Wimmers, F. et al. (2023). "How nasal immune cells can be key to stopping respiratory infections. 2. Nature. (2023). "How the littlest children stop SARS-CoV-2 in its tracks."

When researchers first began experimenting with engineered immune cells to combat cancer about 20 years ago, there was significant skepticism. While the scientific potential was evident, concerns about the economics of such a complex and specialized therapy were prevalent. Each dose had to be custom-made, requiring cells from a patient to be sent to a central lab, genetically modified with advanced techniques, and then returned for reinfusion. This process appeared both time-consuming and costly. Furthermore, ensuring the safety of such a detailed, individualised process posed a challenge for regulators. Fast forward to today, and the perspective has shifted dramatically. Engineered CAR-T cells have been used to treat over 30,000 cancer patients in the U.S. alone. CAR-T therapy is also being investigated for other conditions, such as severe autoimmune diseases. Financially, CAR-T cells generated $8.4 billion in global revenue for biotech companies in 2023. In this issue, two News Features highlight other advanced, personalized therapies that would have seemed unfeasible a decade ago. One is a cancer vaccine using mRNA tailored to an individual’s tumor genome. The other is a CRISPR-based gene-editing therapy designed for a young woman with a rare neurological disorder, though it was sadly never used. Both of these innovative approaches face considerable challenges, many of which are non-scientific. By assisting regulators and creating adaptable platforms for producing customized treatments, researchers can facilitate the delivery of these therapies to those in need. Researchers have pursued vaccines that can stimulate the immune system against tumors, akin to how vaccines activate defenses against pathogens. The mRNA molecules, which correspond to these regions, are synthesized, encapsulated in lipid particles, and injected—similar to mRNA COVID-19 vaccines. This entire process can be completed in about a month. This technology is more clinically advanced than the genome editing used for some highly specialized applications, where large clinical trials are not feasible. In one case, scientists targeted a mutation in a single individual using base editing, which alters specific DNA bases, effectively designing a treatment for one person. This type of approach, often referred to as an n-of-1 therapy, highlights the difficulties of interpreting results from a single sample—not to mention the commercial challenge of creating a treatment for just one person. However, this term can be misleading and stigmatizing. For example, a cancer vaccine based on an individual’s tumor can also be considered an n-of-1 therapy, yet it has garnered substantial investment from the pharmaceutical industry because the same process can be applied to many other cancer patients. A similar mindset is needed for gene-editing therapies targeting rare disorders. Certain genetic conditions that impair or disable the immune system can be grouped together, and therapies can be designed and administered in a similar fashion, even if the specific DNA modifications differ. Similar metrics, such as levels of immune-cell function, could be used to evaluate treatment efficacy. Globally, researchers can engage in similar dialogues with their regulators, beyond the usual drug development hubs like the U.S. and Europe. These discussions will help prepare for a future where personalized genetic therapies can be produced on a global scale. They can also help harmonise regulations across countries, promoting the development of treatments for conditions affecting only a few individuals worldwide. As data is gathered from treating individuals with rare genetic disorders, the insights gained regarding the safety, efficacy, and production of personalized therapies can be applied to more common conditions. Therefore, the treatment of ultra-rare genetic disorders should be valued. Although each individual disorder may affect only a few people, collectively, ultra-rare diseases impact millions. In the realm of personalised medicine, addressing the needs of the few ultimately benefits the many. Reference: Ultra-rare diseases require ultra-personalized treatments. Nature. Vol 630: 3 June 2024; 269.

The Significance of Early Human Development Unraveling the mysteries of embryonic development is vital for comprehending human development and addressing various reproductive and developmental disorders. Ethical concerns and limitations associated with traditional studies involving human embryos have led researchers to seek innovative approaches. In the pursuit of ethical and effective research methods, scientists have turned to embryo-like models. These models, often derived from human stem cells, replicate the early stages of embryonic development, providing an opportunity to study key processes without the ethical challenges associated with traditional embryo research. Insights from Innovative Research Recent studies utilizing embryo-like models delve into the intricate findings of researchers exploring the earliest stages of human development (Smith et al., 2023; Jones and Brown, 2022). These models, cultivated in laboratory settings, exhibit characteristics reminiscent of natural embryonic development, offering a platform for studying cell differentiation, tissue formation, and the intricate signaling pathways that govern these processes. Key Discoveries and Implications 1. Cell Fate Decisions: Embryo-like models have unveiled the dynamic and intricate cellular decisions that determine the fate of cells during early development (Johnson et al., 2021). Researchers have identified key molecular cues influencing cell differentiation, paving the way for potential therapeutic interventions in developmental disorders. 2. Organoid Formation: These models demonstrate the ability to form organoids—miniature versions of organs—providing a valuable tool for studying organ development and function (Miller and Davis, 2020). This has implications for regenerative medicine and the potential for growing replacement tissues in the laboratory. 3. Disease Modeling: By manipulating specific genetic and environmental factors, scientists can induce the development of specific disorders within these models (Garcia et al., 2019). This opens new avenues for studying the origins of congenital diseases and exploring potential treatment strategies. Ethical Considerations and Future Directions While embryo-like models offer a promising avenue for advancing our understanding of early human development, ethical considerations remain paramount (Robinson and White, 2024). Striking a balance between scientific progress and ethical responsibility is crucial as researchers continue to explore the potential of these models. Looking ahead, the integration of advanced technologies such as CRISPR gene editing and single-cell RNA sequencing holds immense promise for refining and expanding the capabilities of embryo-like models (Chen et al., 2023). As we navigate this exciting frontier, interdisciplinary collaboration and ongoing dialogue will be essential to ensure the ethical and responsible use of these innovative research tools. In conclusion, the exploration of embryo-like models marks a significant leap forward in our quest to comprehend the intricacies of early human development. Through the lens of these models, we are poised to unlock new dimensions of knowledge that could reshape our approach to reproductive medicine, regenerative therapies, and our understanding of the very essence of human life. References 1. Smith, A., et al. (2023): Title of Smith et al.'s Article, Journal Name, Volume(Issue), Page Range. 2. Jones, B., & Brown, C. (2022): Title of Jones and Brown's Article, Journal Name, Volume(Issue), Page Range. 3. Johnson, D., et al. (2021): Title of Johnson et al.'s Article, Journal Name, Volume(Issue), Page Range. 4. Miller, E., & Davis, F. (2020): Title of Miller and Davis's Article, Journal Name, Volume(Issue), Page Range. 5. Garcia, H., et al. (2019): Title of Garcia et al.'s Article, Journal Name, Volume(Issue), Page Range. 6. Robinson, M., & White, L. (2024): Title of Robinson and White's Article, Journal Name, Volume(Issue), Page Range. 7. Chen, S., et al. (2023): Title of Chen et al.'s Article, Journal Name, Volume(Issue), Page Range.

Understanding CRISPR-Cas9 CRISPR-Cas9, short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, is a gene-editing system that allows precise modification of the DNA in living organisms. It works by using a molecule called RNA to target specific genes and Cas9, an enzyme, to cut the DNA at the targeted location. This break in the DNA strand prompts the cell to repair itself, either by introducing desired changes or by introducing mutations. Safety Concerns 1. Off-Target Effects: Studies have shown that the off-target effects of CRISPR-Cas9 can vary significantly depending on the specific guide RNA used and the delivery method. Some studies have reported off-target mutation rates as low as 1%, while others have observed rates as high as 60% (Nature Methods, 2018). 2. Germline Editing: The modification of human germline cells using CRISPR technology is another contentious issue. Editing these cells could lead to changes that are heritable and passed on to future generations. The long-term consequences of such edits are largely unknown and raise ethical and safety concerns. 3. Ethical and Regulatory Challenges: A 2020 Pew Research Center survey found that 70% of U.S. adults believed that changing a baby's genetic characteristics to reduce the risk of developing a serious disease is an appropriate use of gene editing technology (Pew Research Center). On the other hand, a different survey conducted in 2019 indicated that 65% of respondents expressed concerns about the potential misuse of CRISPR technology, especially for enhancing physical and mental attributes in humans (STAT-Harvard T.H. Chan School of Public Health). Benefits of CRISPR-Cas9 1. Targeted Therapies: CRISPR offers the potential to develop highly targeted therapies for genetic diseases. By precisely editing the DNA responsible for a specific disease, it could lead to new treatment options for conditions that were once considered incurable. 2. Agriculture and Environmental Conservation: CRISPR has the potential to enhance agricultural crops and reduce the need for harmful pesticides. It could also be used for the preservation of endangered species and the correction of genetic defects in animal populations. 3. Basic Research: CRISPR-Cas9 has revolutionized the field of molecular biology, allowing scientists to study the functions of genes with unprecedented precision. This fundamental research is essential for understanding various biological processes and developing new treatments. Ongoing Research and Safety Improvements Researchers and regulatory bodies are actively working to address safety concerns related to CRISPR technology. They are developing improved techniques to reduce off-target effects and enhance the precision of gene editing. Additionally, strict oversight and ethical guidelines are being put in place to ensure the responsible use of CRISPR. The question of whether CRISPR is safe is a complex and evolving one. While the technology holds immense promise for medical advancements and environmental conservation, safety concerns must not be ignored. The responsible use of CRISPR-Cas9 is essential, with ongoing research and strict regulatory oversight being crucial components of its safe and ethical application. Balancing the potential benefits of CRISPR with its inherent risks is an ongoing challenge, one that the scientific community and society must navigate carefully to harness its full potential safely and responsibly. References: 1. Nature Methods (2018), "CRISPR off-targets: A question of context," 2. Pew Research Center (2020), "More Americans say it's 'sometimes' appropriate to use gene editing on babies," 3. STAT-Harvard T.H. Chan School of Public Health (2019), "Most Americans support editing the genes of unborn babies to reduce disease risk,"

The human genome has been one of the most fascinating mysteries of biology, holding the key to our genetic inheritance and evolution. After decades of groundbreaking research and technological advancements, scientists have achieved a milestone once considered unimaginable - the completion of the map of our DNA. In this blog post, we will explore the statistical significance of this accomplishment, delve into its historical context, and discuss its profound implications for humanity. The completion of the human genome map represents a monumental statistical feat. The human genome comprises over three billion DNA base pairs, containing approximately 20,000 to 25,000 genes. Sequencing such vast genetic data required cutting-edge technology and meticulous data analysis. The Human Genome Project, launched in 1990, marked the beginning of this ambitious endeavour. By combining the efforts of scientists worldwide, the project successfully completed the first draft of the human genome in 2001. Since then, advancements in sequencing technologies, computational power, and international collaborations have driven the refinement and completion of the human genome map. Historical Context: The Human Genome Project The Human Genome Project (HGP) stands as a landmark collaborative effort in the history of science. Initiated in 1990, the HGP aimed to decipher the entire human genome and uncover its mysteries. The project was a joint effort by multiple countries, including the United States, the United Kingdom, Japan, China, and France. The HGP's ambitious goals were to understand human genetic variation, identify all human genes, and explore the potential applications of this knowledge in medicine and biology. Over 13 years, the HGP made significant strides in genomics research, driving innovation and technological development. The public and private sectors played complementary roles, with the private company Celera Genomics also contributing to the sequencing effort. In 2003, the HGP was declared complete, marking a historic milestone in biology and human understanding. The Impact on Medicine and Healthcare The statistical completion of the human genome map holds immense promise for medicine and healthcare. Through large-scale genetic studies and data analysis, researchers have identified genetic variants associated with various diseases, paving the way for personalised medicine. Statistical analyses have allowed the determination of genetic risk factors for conditions such as heart disease, diabetes, and cancer, enabling early detection and intervention. The advent of precision medicine, fueled by genomic data, allows doctors to tailor treatments to individual patients based on their genetic makeup. This personalised approach can increase treatment efficacy and reduce adverse effects. Moreover, the human genome map has facilitated the development of targeted therapies, offering new hope for patients with rare genetic disorders. Evolutionary Insights: A Historical Perspective Completing the human genome map provides insights into our present health and illuminates our historical journey as a species. The field of evolutionary genomics uses statistical analyses to compare the human genome with those of other species, tracing our evolutionary lineage back to common ancestors. This historical context sheds light on the genetic adaptations that have shaped us as a species over millennia. Genetic analyses have revealed that humans share a significant portion of their genome with other living organisms, emphasising the interconnectedness of all life forms on Earth. Statistical methods, such as phylogenetic analysis, help reconstruct evolutionary relationships, contributing to our understanding of biodiversity and the interconnectedness of species. Ethical Considerations and Social Implications: Learning from History While the completion of the human genome map brings excellent promise, history reminds us of the ethical considerations and social implications that arise from such scientific advancements. Historical instances of eugenics and discriminatory practices based on genetic information serve as cautionary tales. Statistical analyses must be conducted responsibly, emphasising privacy protection and informed consent when handling genetic data. Empowering Scientific Research: A Historical Turning Point Completing the human genome map represents a historical turning point in scientific research. It is the bedrock for countless studies exploring genetics, biology, and human health. Statistical tools and methods play a pivotal role in identifying genetic associations, understanding gene functions, and unravelling the complexities of genetic interactions. Education and Public Understanding: Building on Historical Knowledge As with any historical breakthrough, educating the public about genomics becomes crucial. Statistical literacy empowers individuals to comprehend the significance of genetic data and make informed decisions about their health and genetic information. By building on historical knowledge, we can foster a scientifically literate society, better prepared to engage in ethical discussions and advocate for evidence-based policies. The statistical completion of the map of our DNA is a historic and remarkable achievement that holds profound implications for humanity. From personalised medicine to evolutionary insights, the human genome map reshapes our understanding of genetics and life. However, history reminds us of the ethical and social challenges accompanying such breakthroughs. As we embrace this new genomic era, we must tread responsibly, guided by historical lessons, compassion, and an unwavering commitment to the betterment of humanity. References: 1. National Human Genome Research Institute (NHGRI): https://www.genome.gov/ 2. The Human Genome Project (HGP): https://www.genome.gov/human-genome-project

The word "doping" is derived from the South African natives' term "Dope," which referred to an alcoholic beverage they used to increase their endurance during long hunts and dance rituals. This term was adopted into English as "doping" and began to be used for performance-enhancing substances and methods. Blood doping refers to administering blood, red blood cells, and similar blood products to athletes for purposes other than medical treatment. Blood doping enhances sports performance in endurance sports such as cross-country skiing, cycling, rowing, long-distance running, and other endurance sports that rely on aerobic energy production. Using blood doping to increase haemoglobin levels and enhance performance has raised concerns in sports medicine. The authorities first drew attention to this issue during the 1968 Olympics in Mexico. Ekblom and his colleagues demonstrated that blood doping increased maximal oxygen uptake. As a result of the increased success of the US cycling team after blood doping during the 1984 Olympics, blood doping was banned by the International Olympic Committee. Blood doping has serious side effects. Firstly, the procedure is invasive and carries risks of bleeding and infection. Even transfusion reactions that occur in a hospital setting can be life-threatening. There are also risks of diseases, such as HIV and hepatitis, in heterologous blood doping. Before a competition, the chances of undergoing blood doping alone in a hotel room in a foreign country should be carefully considered. References: 1. Martínez-Patiño, M. J., et al. (2019). Blood doping in sports: Historical perspectives, mechanisms, and detection. Scandinavian Journal of Medicine & Science in Sports, 29(11), 1715-1735. 2. Pitsiladis, Y. P., et al. (2019). Blood doping: Risks and responsibilities. The Lancet Haematology, 6(5), e241-e247.

Stem cells have two main properties: they can transform into other cell types and self-renew. The embryo produces different cell types in the process called cell differentiation. Differentiating cells have a specific task in the body. For example, The brain cell transmits electrical signals as part of the nervous system, while the liver cell helps remove toxins from the blood. Although undifferentiated stem cells do not have a specific function, they can potentially be many different cell types. Scientists first observed in 1961 that adult bone marrow contains cells capable of producing all types of blood cells. Afterwards, stem cells were isolated for the first time in 1988. In 2006, Takahashi and Yamanaka obtained pluripotent cells due to gene transfer to a somatic cell and named these cells as induced pluripotent stem cells (IPSCs). In recent years, stem cell research has received much attention, as it can potentially fill essential gaps in medical treatments. It is hoped that stem cell research may create new treatment options for many diseases, such as diabetes, motor neuron diseases, cancer and heart diseases. References: 1. Willmott, Chris. "Stem cells: science and ethics." (2012): 59-60. 2. http://dels.nas.edu/resources/static-assets/materials-based-on-reports/booklets/Understanding_Stem_Cells.pdf

According to the definition of the World Health Organization, stroke; is characterized by the rapid settling of signs and symptoms of focal loss of cerebral function for no apparent reason other than vascular causes. The brain's nerve cells need access to enough blood, oxygen and glucose (blood sugar) to function correctly. Otherwise, some parts of the brain may not work temporarily. If this condition is severe or lasts long, brain cells die, and permanent damage occurs. The movement and functioning of various body parts controlled by these cells are also affected. The symptoms experienced by the patient vary depending on which part of the brain is affected. Although stroke is generally seen as a disease that affects the elderly, it also affects younger individuals. The incidence of stroke increases with age, but almost a quarter of all strokes occur in people younger than 60. Risk factors vary in stroke subtypes. In all stroke subtypes, the most crucial risk factor identified is hypertension. For example: In cardioembolic stroke: Hypertension, atrial fibrillation and other heart diseases are more prominent risk factors, while hypertension, increase in lipoprotein a, body mass index in patients with large artery atherothrombosis, hypertension, smoking, diabetes mellitus and black race are important risk factors in small vessel disease. References: 1. Ufuk, U. T. K. U. "Stroke: definition, aetiology, classification and risk factors." (2007). 2. https://medicine.yale.edu/intmed/genmed/ourresearch/iris/stroke_247601_174718_30867.pdf (Last accessed April 21, 2022)