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What is it and what does it do? Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The role of dopamine in the movement and the reward pathway 01/04/26, 11:26 Last updated: Published: 21/09/24, 15:59 What is it and what does it do? Dopamine is a neurotransmitter produced mainly in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNPC) in the brain, exhibiting both excitatory and inhibitory effects in different brain pathways. ( About 50% of body’s dopamine is also produced in the gut). Dopamine is important in mediating the mesolimbic and nigrostriatal pathways for reward and movement, respectively. Therefore, damage to dopaminergic neurones affects dopamine levels in the brain and can consequently result in diseases associated with abnormal dopamine levels. Movement The role of dopamine is vital in modulating the initiation of movement through both the direct and indirect pathways of the basal ganglia ( Figure 1 ). In the direct pathway, dopamine produced from the SNPC binds to the D1 Gs-coupled receptors in the striatum resulting in the activation of the intracellular signalling cascade. Activation of these receptors results in increased intracellular cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) levels, which control the modulation of ion channels, including calcium channels for further depolarisation of the striatal cells. The excitation of the striatum results in GABAergic inhibition of the globus pallidus internal segment (GPI) and the substantia nigra pars reticulata (SNPR). Hence, this results in the disinhibition of the thalamus, allowing for excitatory glutamatergic transmission to the motor cortex for the facilitation of movement. The activation of the striatum via D1 receptor stimulation can be supported by a study conducted by Gerfen et al. 2012 in which they concluded that PKA activates calcium voltage-gated 1 L-type calcium channels, resulting in depolarisation of striatal cells, which causes the enablement of movement via the direct pathway. However, in the indirect pathway, dopamine binds to D2 Gi-coupled receptors with a higher affinity than D1 receptors, causing inhibition of these receptors and their intracellular signalling cascades. Consequently, there is decreased inhibition of potassium channels by the second messengers, resulting in hyperpolarisation due to potassium efflux from the striatal cells. As the striatum is inactivated, this reduces the overall inhibitory effect of the indirect pathway on the thalamus, allowing for movement. Therefore, dopamine is critical for the normal functioning of humans by allowing them to control their movements for survival, for example, by pushing a ball away when it is about to hit them. Reward pathway The mesolimbic dopaminergic pathway ( Figure 2 ) is the most recognised reward pathway in the brain. This pathway contains the VTA, located in the midbrain, the nucleus accumbens (NA) and the tuberculum olfactorium (TO), located in the basal forebrain. The lateral regions of the VTA are the most abundant in A10 dopaminergic neurones in comparison to other regions of the VTA. These A10 neurones are activated in association with reward anticipation, for example, after exercising. The medial VTA dopaminergic neurones project to the core and medial shell regions of the NA, and the lateral VTA project towards the lateral shell region of the NA (figure 3). Thus, increasing dopamine levels in the NA and inducing the processing of the reward. Moreover, dopaminergic inputs from the VTA to the TO allow the individual to develop an odour preference for a specific stimulus due to motivation-oriented behaviour. Hence, this could be a reason why the anticipation of eating one's favourite food by evoking the memory of its smell is associated with the feeling of reward. Experiments conducted by FitzGerald et al. 2014 support my points regarding the role of the TO in the mesolimbic pathway. In their study, mice were given a choice of two different odours to choose from. The team noted activation of c-Fos neurones in the forebrain, indicating neuronal activity in this region, which is involved in reward motivation behaviour. Hence, allowing them to support the importance of the TO in odour processing and reward behaviour in the mice when choosing a more pleasurable odour. Eventually, projections from the TO and NA converge at the ventral pallidum, where the enrichment of reward-related learning occurs. Therefore, dopamine is essential for the initiation of the reward pathway in ensuring the continuation of reward behaviour when exposed to a specific stimulus and for survival due to the association of reproduction with reward. Conclusion In conclusion, dopamine is essential for the initiation of movement and in the reward pathway for normal human functioning and survival. Studies into aldehyde-dehydrogenase 1 in the SNPC have found that it protects dopaminergic neurones against neurodegeneration. Further studies will aid in understanding the mechanisms by which this enzyme is regulated and the actions by which it protects dopaminergic neurones in the SNPC. Written by Maria Z Kahloon Related articles: The dopamine connection between the gut and the brain / Interplay of hormones and microbiome / Types of movement Project Gallery

An extensive collection of insightful reviews on the best STEM books available. Whether you're a student looking to deepen your knowledge or something to aid your revision and research, an educator seeking great resources for your classroom, or simply a curious mind passionate about science, technology, engineering, mathematics, medicine and more, you'll find something here to inspire and inform you.  Discover Your Next Great Read Deep Dive into STEM Books Here you can explore an extensive collection of insightful reviews on the best STEM books available. Whether you're a student looking to deepen your knowledge or something to aid or complement your revision and research, an educator seeking great resources for your classroom, or simply a curious mind passionate about science, technology, engineering, mathematics, medicine and more, you'll find something here to inspire and inform you. Our Curated Selections: Intern Blues by Robert Marion, M.D. The Emperor of All Maladies by Siddhartha Mukherjee The Molecule by Dr Rick Sax and Marta New

Scientia News is full of STEM blogs, articles and resources freely available across the globe for students. Browse all of our fascinating content written by students and professionals showing their passion in STEM and the other sciences. Log In Welcome to Scientia News DELIVERING INFORMATIVE CONTENT Scientia News is full of STEM blogs, articles and resources freely available across the globe for students. Browse all of our fascinating content written by students and professionals showing their passion in STEM and other sciences. We hope this platform helps you discover something that inspires your curiosity, and encourages you to learn more about important topics in STEM. Meet the Official Team NAVIGATE AND CLICK THE PHOTOS BELOW TO LEARN MORE ABOUT US! To play, press and hold the enter key. To stop, release the enter key. To play, press and hold the enter key. To stop, release the enter key. To play, press and hold the enter key. To stop, release the enter key. Latest Articles chemistry Molecular blueprints: the synthesis of ibuprofen View More chemistry Looking at the rare earth elements View More biology Ethnic Health Inequalities View More pharmacology The promising effects of magic mushrooms for depression View More CONTACT CONTACT US Scientia News welcomes anyone who wants to share their ideas and write for our platform. If you are interested in realising your writing potential with us AND live in the UK; and/ or would like to give feedback: Email us at scientianewsorg@gmail.com or fill in our GET IN TOUCH form below and we'll be in contact... Follow us on our socials for the latest updates. Comment, like and share! Join our mailing list below for latest site content. You can also sign up to become a site member . SUBSCRIPTION Join our mailing list to receive alerts for new articles and other site content. Be sure to check your spam/ junk folders in case emails are sent there. Email Subscribe GET IN TOUCH First Name Last Name Email Message Send Thanks for submitting!

How your gut influences your mood and behaviour Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The dopamine connection 01/04/26, 11:27 Last updated: Published: 25/03/24, 12:01 How your gut influences your mood and behaviour Introduction to dopamine Dopamine is a neurotransmitter derived from an amino acid called phenylalanine, which must be obtained through the diet, through foods such as fish, meat, dairy and more. Dopamine is produced and released by dopaminergic neurons in the central nervous system and can be found in different brain regions. (About 50% of body’s dopamine is also produced in the gut). The neurotransmitter acts via two mechanisms: wiring transmission and volume transmission. In wiring transmission, dopamine is released to the synaptic cleft and acts on postsynaptic dopamine receptors. In volume transmission, extracellular dopamine arrives at neurons other than postsynaptic ones. Through methods such as diffusion, dopamine then reaches receptors in other neurons that are not in direct contact with the cell that has released the neurotransmitter. In both mechanisms, dopamine binds to the receptors, transmitting signals between neurons and affecting mood and behaviour. The link between dopamine and gut health Dopamine has been known to result in positive emotions, including pleasure, satisfaction and motivation, which can be influenced by gut health. Therefore, what you eat and other factors, including motivation, could impact your mood and behaviour. This was proven by a study (Hamamah et al., 2022), which looked at the bidirectional gut-brain connection. The study found that gut microbiota was important in maintaining the concentrations of dopamine via the gut-brain connection, also known as the gut microbiota-brain axis or vagal gut-to-brain axis. This is the communication pathway between the gut microbiota and the brain facilitated by the vagus nerve, and it is important in the neuronal reward pathway, which regulates motivational and emotional states. Activating the vagal gut-to-brain axis, which leads to dopamine release, suggests that modulating dopamine levels could be a potential treatment approach for dopamine-related disorders. Some examples of gut microbiota include Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium, Enterococcus, and Ruminococcus , and they can affect dopamine by modulating dopaminergic activity. These gut microbiota are able to produce neurotransmitters, including dopamine, and their functions and bioavailability in the central nervous system and periphery are influenced by the gut-brain axis. Gut dysbiosis is the disturbance of the healthy intestinal flora, and it can lead to dopamine-related disorders, including Parkinson's disease, ADHD, depression, anxiety, and autism. Gut microbes that produce butyrate, a short-chain fatty acid, positively impact dopamine and contribute to reducing symptoms and effects seen in neurodegenerative disorders. Dopamine as a treatment It is important to understand the link between dopamine and gut health, as this could provide information about new therapeutic targets and improve current methods that have been used to prevent and restore deficiencies in dopamine function in different disorders. Most cells in the immune system contain dopamine receptors, allowing processes such as antigen presentation, T-cell activation, and inflammation to be regulated. Further research into this could open up a new possibility for dopamine to be used as a medication to treat diseases by changing the activity of dopamine receptors. Therefore, dopamine is important in various physiological processes, both in the central nervous and immune systems. For example, studies have shown that schizophrenia can be treated with antipsychotic medications which target dopamine neurotransmission. In addition, schizophrenia has also been treated by targeting the dysregulation (decreasing the amount) of dopamine transmission. Studies have shown promising results regarding dopamine being used as a form of treatment. Nevertheless, further research is needed to understand the interactions between dopamine, motivation and gut health and explore how this knowledge can be used to create medications to treat conditions. Conclusion The bidirectional gut-brain connection shows the importance of gut microbiota in controlling dopamine levels. This connection influences mood and behaviour but also has the potential to lead to new and innovative dopamine-targeted treatments being developed (for conditions including dopamine-related disorders). For example, scientists could target and manipulate dopamine receptors in the immune system to regulate the above mentioned processes: antigen presentation, T-cell activation, and inflammation. While current research has shown some promising results, further investigations are needed to better comprehend the connection between gut health and dopamine levels. Nevertheless, through consistent studies, scientists can gain a deeper understanding of this mechanism to see how changes in gut microbiota could affect dopamine regulation and influence mood and behaviour. Written by Naoshin Haque Related articles: the gut microbiome / Crohn's disease / Microbes in charge Project Gallery

Discussing why people with PTSD have intrusive memories Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Boom, and You're Back! 01/04/26, 11:23 Last updated: Published: 19/01/24, 12:14 Discussing why people with PTSD have intrusive memories This is Part I in a two-part series on PTSD and intrusive memories. Next article: PTSD and Tetris Post-traumatic stress disorder (PTSD) is an anxiety disorder which may develop if a person has been involved in or witnessed a stressful event. Whilst most people associate PTSD with soldiers, it also develops in people like you and me. In fact, many events that lead to PTSD development occur in everyday life, such as car crashes, traumatic childbirth, assaults, robberies etc. One of the main symptoms of PTSD is intrusive memories. This is when people involuntarily develop recollections of the event within their consciousness. Dual modality theory The main model which explains the development of intrusive memories in PTSD is the Dual Representation Theory (DRT). DRT was proposed by Brewin, Dalgleish, and Joseph, and this idea suggests that there are two separate memory systems which encode information during an event. The verbally accessible memory system (VAM) holds information about the conscious experience of the event meaning it can be voluntarily recalled afterwards. This is compared to the situationally accessible memory system (SAM) which processes unconscious sensory information, like smells and sounds, which cannot be voluntarily recalled. The theory suggests VAM is impaired and focuses on the frightening information and the fear that we experience during an event, and this affects how we process the information. Coupled with the vivid sensory information captured by SAM, when individuals are in a context where physical or sensory features are like the traumatic event, they unconsciously trigger intrusive memories which are highly distressing and emotionally valanced. Think of the last movie you watched about someone returning from war who was scared of fireworks. Now you understand that the banging sound triggers the highly emotional memories from the SAM and VAM system, forcing them to re-witness situations where a bomb has gone off. One loud boom and they are back in a war zone. Where in the brain is this going on? There are many brain areas involved in PTSD memory processing, but some common areas are associated with the formation and retrieval of traumatic memories. Hippocampus: combines lots of information in the environment into one memory that can be consciously retrieved. It seems likely that this area is essential for creating verbally accessible memories in trauma, so is part of the VAM system. Ventromedial prefrontal cortex: involved in regulating how much emotion is encoded into a memory. It has been said that dysfunction in this area is why people with PTSD have difficulties processing the emotion attached to the traumatic event. Amygdala: Important in how we learn to associate stimuli with the correct emotional response. It has been said in highly stressful events the amygdala becomes hyperactive which is why there is such a strong emotional reaction to certain cues, therefore is likely to be crucial in the SAM system. Hormones: elevated levels of glucocorticoids, cortisol, and norepinephrine can influence the consolidation of memories which creates stronger and more persistent traumatic memories. Written by Alice Jayne Greenan Related articles: Synaptic plasticity / Can you erase your memory? Project Gallery

A hereditary neurodegenerative disorder Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Huntington's disease 25/03/26, 16:52 Last updated: Published: 18/10/23, 16:12 A hereditary neurodegenerative disorder Huntington’s disease (HD) is a neurodegenerative disorder causing cognitive decline, behavioural difficulties, and uncontrollable movements. It is a hereditary disease that has a devastating effect on the individual’s life and unfortunately is incurable. Genetic component What may come as a surprise, is that in everyone’s genetics there are two copies (one from each parent) of the Huntingtin’s gene coding for the Huntingtin protein. This gene is coded by CAG repeats. In healthy genes, the CAG sequence is repeated between 10 and 26 times. However, if the gene is faulty, CAG repeats over 40 times resulting in a dysfunctional Huntingtin protein. The disease is autosomal dominant meaning regardless of gender, if either parent is a carrier, their child has a 50% chance of inheriting the faulty gene. REMINDER: because the gene is dominant, it means those who inherit even one copy will develop the disease Effect on the brain The faulty Huntingtin protein accumulates in cells, leading to cell death and damage to the brain. If you were to look at the brains of individuals with Huntington’s Disease, you would see a reduction in volume of the caudate and putamen. These areas are part of the striatum, which is a subdivision of the basal ganglia, involved in fine tuning our voluntary movements, i.e., reaching out to grab a cup. As the disease progresses, this atrophy can extend to other areas of the brain including the thalamus, frontal lobe, and cerebellum. Symptoms The symptoms normally manifest in three categories: motor, cognitive and psychiatric. We know that the basal ganglia is involved in our voluntary movement, so the damage causes one of the most visible symptoms in HD- uncontrollable and jerky movements. Cognitive symptoms include personality changes, difficulties with planning and attention. There can also be impairments to how those with HD recognise emotions- all these symptoms can interact to make social interaction more difficult. Finally, the psychiatric symptoms often seen include irritability and aggression, depression, anxiety, and apathy. Impact on life and family At the age when diagnosis usually occurs (around 30 years old), patients are often buying houses, getting married and either having children or deciding to start a family. The diagnosis may change people's outlook on having children and can put a great psychological burden on them if they have unknowingly passed it along to those already born. Diagnosis also brings consequences to seemingly mundane, but incredibly important, issues such as gaining life insurance, with some companies not covering individuals with an official diagnosis. Subsequently this makes life harder for their families, as the patient will eventually be unable to work and there could be associated costs with the need for care facilities as the disease progresses. Unfortunately, this is a progressive neurodegenerative condition with no cure. The only treatment options available at present, are interventions which aim to alleviate the patients’ symptoms. Whilst these treatments will reduce the motor and psychiatric symptoms, they cannot stop the progression of Huntington’s disease. We have only scratched the surface on the impact Huntington’s disease has on a patient and their families. It is so important to understand ways in which everyone that is affected can be best supported during the disease progression, to give all those involved a better quality of life. Written by Alice Jayne Greenan Related articles: A potential gene therapy for HD / Epilepsy Project Gallery

Deconstructing allergies: mechanisms, treatments, and prevention Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Allergies 08/07/25, 16:24 Last updated: Published: 13/05/24, 14:27 Deconstructing allergies: mechanisms, treatments, and prevention Modern populations have witnessed a dramatic surge in the number of people grappling with allergies, a condition that can lead to a myriad of health issues such as eczema, asthma, hives, and, in severe cases, anaphylaxis. For those who are allergic, these substances can trigger life-threatening reactions due to their abnormal immune response. Common allergens include antibiotics like penicillin, as well as animals, insects, dust, and various foods. The need for strict dietary restrictions and the constant fear of accidental encounters with allergens often plague patients and their families. Negligent business practices and mislabelled food have even led to multiple reported deaths, underscoring the gravity of allergies and their alarming rise in prevalence. The primary reason for the global increase in allergies is believed to be the lack of exposure to microorganisms during early childhood. The human microbiome, a collection of microorganisms that live in and on our bodies, is a key player in our immune system. The rise in sanitation practices is thought to reduce the diversity of the microbiome, potentially affecting immune function. This lack of exposure to infections may cause the immune system to overreact to normally harmless substances like allergens. Furthermore, there is speculation about the impact of vitamin D deficiency, which is becoming more common due to increased indoor time. Vitamin D is known to support a healthy immune response, and its deficiency could worsen allergic reactions. Immune response Allergic responses occur when specific proteins within an allergen are encountered, triggering an immune response that is typically used to fight infections. The allergen's proteins bind to complementary antigens on macrophage cells, causing these cells to engulf the foreign substance. Peptide fragments from the allergen are then presented on the cell surface via major histocompatibility complexes (MHCs), activating receptors on T helper cells. These activated T cells stimulate B cells to produce immunoglobulin E (IgE) antibodies against the allergen. This sensitizes the immune system to the allergen, making the individual hypersensitive. Upon re-exposure to the allergen, IgE antibodies bind to allergen peptides, activating receptors on mast cells and triggering the release of histamines into the bloodstream. Histamines cause vasodilation and increase vascular permeability, leading to inflammation and erythema. In milder cases, patients may experience itching, hives, and runny nose; however, in severe allergic reactions, intense swelling can cause airway constriction, potentially leading to respiratory compromise or even cessation. At this critical point, conventional antihistamine therapy may not be enough, necessitating the immediate use of an EpiPen to alleviate symptoms and prevent further deterioration. EpiPens administer a dose of epinephrine, also known as adrenaline, directly into the bloodstream when an individual experiences anaphylactic shock. Anaphylactic shock is typically characterised by breathing difficulties. The primary function of the EpiPen is to relax the muscles in the airway, facilitating easier breathing. Additionally, they counteract the decrease in blood pressure associated with anaphylaxis by narrowing the blood vessels, which helps prevent symptoms such as weakness or fainting. EpiPens are the primary treatment for severe allergic reactions leading to anaphylaxis and have been proven effective. However, the reliance on EpiPens underscores the necessity for additional preventative measures for individuals with allergies before a reaction occurs. Preventative treatment Young individuals may have a genetic predisposition to developing allergies, a condition referred to as atopy. Many atopic individuals develop multiple hypersensitivities during childhood, but some may outgrow these allergies by adulthood. However, for high-risk atopic children, preventive measures may offer a promising solution to reduce the risk of developing severe allergies. Clinical trials conducted on atopic infants explored the concept of immunotherapy treatments, involving continuous exposure to small doses of peanut allergens to prevent the onset of a full-blown allergy. Initially, skin prick tests for peanut allergens were performed, and only children exhibiting negative or mild reactions were selected for the trial. Those with severe reactions were excluded due to the high risk of anaphylactic shock with continued exposure. The remaining participants were randomly assigned to either consume peanuts or follow a peanut-free diet. Monitoring these infants as they aged revealed that continuous exposure to peanuts reduced the prevalence of peanut allergies by the age of 5. Specifically, only 3% of atopic children exposed to peanuts developed an allergy compared to 17% of those in the peanut-free group. The rise in severe allergies poses a growing concern for global health. Once an atopic individual develops an allergy, mitigating their hypersensitivity can be challenging. Current approaches often involve waiting for children to outgrow their allergies, overlooking the ongoing challenges faced by adults who remain highly sensitive to allergens. Implementing preventive measures, such as early exposure through immunotherapy, could enhance the quality of life for future generations and prevent sudden deaths in at-risk individuals. In conclusion, a dramatic surge in the prevalence of allergies in modern populations requires more attention from researchers and health care providers. Living with allergies can bring many complexities into someone’s life even before they potentially have a serious reaction. Currently treatments are focused on post-reaction emergency care, however preventative strategies are still a pressing need. With cases of allergies predicted to rise further, research into this global health issue will become increasingly important. There are already promising results from early trials of immunotherapy treatments, and with further research and implementation these treatments could improve the quality of life of future generations. Written by Charlotte Jones Related article: Mechanisms of pathogen evasion Project Gallery

Mutations in collagen and related proteins are the primary cause of EDS Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link From genes to joints: how Ehlers-Danlos Syndrome is shaped by genetics 12/09/25, 11:12 Last updated: Published: 08/11/24, 11:40 Mutations in collagen and related proteins are the primary cause of EDS This is article no. 10 in a series on rare diseases. Next article: CEDS- a break in cell death . Previous article: Breaking down Tay-Sachs . Ehlers-Danlos Syndrome (EDS) is a group of 13 inherited disorders that affect connective tissues, particularly collagen. Collagen is a crucial protein in the body that provides structure and strength to skin, joints, and blood vessels. Mutations in collagen or collagen-modifying proteins are the primary cause of the types of EDS. EDS manifests through a range of symptoms that vary significantly depending on the specific type of EDS. However, there are common symptoms that many individuals with EDS experience, particularly related to joint and skin issues. For instance, joints can move beyond the normal range, leading to frequent dislocations and subluxations, also called joint hypermobility. Additionally, the skin can be stretched more than usual, which creates a soft and velvety appearance known as skin hyperextensibility. As mentioned in Figure 1 , skin bruising, scarring and tearing are common symptoms, leading to individuals often experiencing chronic pain. Life expectancy for individuals with EDS varies depending on the type of disorder an individual has. This is due to how specific forms can have structural changes in organs and tissues, which can lead to serious life-threatening complications. For example, vascular EDS (vEDS) is associated with a significantly reduced life expectancy due to the risk of spontaneous rupture of major blood vessels, intestines, and other hollow organs. Most other forms of EDS, such as classical EDS (cEDS), hypermobile EDS (hEDS), and kyphoscoliotic EDS (kEDS), generally do not significantly affect life expectancy. However, the health complications that patients have can substantially impact their quality of life. Genetic basis As stated, the various types of EDS encompass many genetic defects, for example, cEDS is linked to mutations in the COL5A1 or COL5A2 genes, which encode the α1 and α2 chains of type V collagen. Following an autosomal dominant inheritance pattern, 50% of cEDS diagnoses inherit the condition from an affected parent, while the other half from a new (de novo) pathogenic variant. Diagnosing EDS encompasses a variety of methods. Firstly, differential diagnosis may be used to distinguish between subtypes like cEDS and hEDS by evaluating clinical features such as the presence of joint hypermobility, skin characteristics, and scarring patterns. Clinicians use these specific symptoms along with family history to differentiate between the subtypes since some, like hEDS, lack identified genetic markers, making this clinical assessment essential for accurate diagnosis and management. This process helps exclude other conditions and accurately identify the EDS subtype. Also, suggestive clinical features identifying pathogenic or likely pathogenic variants in the COL5A1 or COL5A2 genes can be done through molecular genetic testing. This testing can be approached in two ways: targeted multigene panels, which focus on specific genes like COL5A1 and COL5A2 . Alternatively, comprehensive genomic testing, such as exome or genome sequencing, does not require preselecting specific genes and is useful when the clinical presentation overlaps with other inherited disorders. Mutations in COL5A1 and COL5A2 can include missense, nonsense, splice site variants, or small insertions and deletions, all of which impair the function of type V collagen. Missense mutations result in the substitution of one amino acid for another, disrupting the collagen triple helix structure and affecting its stability and function. On the other hand, nonsense mutations lead to a premature stop codon, producing a truncated and usually non-functional protein. Splice site mutations interfere with the normal splicing of pre-mRNA, resulting in aberrant proteins. These mutations in COL5A1 and COL5A2 lead to the characteristic features of cEDS, such as highly elastic skin and joint hypermobility. Furthermore, different types of EDS are caused by specific genetic mutations, each affecting collagen in distinct ways and necessitating varied treatment approaches. VEDS is caused by mutations in the COL3A1 gene, which affects type III collagen and leads to fragile blood vessels and a higher risk of organ rupture. kEDS results from mutations in the PLOD1 or FKBP14 genes, impacting collagen cross-linking, and presents with severe scoliosis and muscle hypotonia. Arthrochalasia EDS (aEDS), due to mutations in the COL1A1 or COL1A2 genes that affect type I collagen, features severe joint hypermobility and congenital hip dislocation. Dermatosparaxis EDS (dEDS) is caused by mutations in the ADAMTS2 gene, which is crucial for processing type I collagen, leading to extremely fragile skin and severe bruising. Each type of EDS highlights the critical role of specific genetic mutations in the structural integrity and function of collagen, which consequently influences treatment approaches. Treatment Treatments for EDS primarily focus on managing symptoms and preventing complications due to the underlying genetic defects affecting collagen. Pain relief through nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and sometimes opioids is common, addressing chronic pain related to joint and muscle issues. Moreover, physical therapy may help strengthen muscles around hypermobile joints, reducing the risk of dislocations and improving stability. Orthopaedic interventions, such as braces and orthotics, are also used to support joint function, and surgery may be considered in severe cases. Cardiovascular care is crucial, especially for vEDS, involving regular monitoring with imaging techniques to detect arterial problems early. Preventive vascular surgery might be necessary to repair aneurysms or other vascular defects. Wound care includes using specialised dressings to handle fragile skin and prevent extensive scarring, relevant to mutations in genes like COL5A1 and COL5A2 in classical EDS. Understanding the specific genetic mutations helps tailor these treatments to address the particular collagen-related defects and associated complications in different EDS types. Moreover, clinical trials for treating EDS have shown both positive and negative results. For example, trials investigating the efficacy of physical therapy in strengthening muscles around hypermobile joints have shown positive outcomes in reducing joint instability and improving function. On the other hand, trials aiming to directly modify the underlying genetic defects in collagen production have faced significant challenges. Gene therapy approaches and other experimental treatments targeting specific mutations, such as those in COL5A1 or COL3A1 genes, have shown limited success and faced hurdles in achieving sufficient therapeutic benefit without adverse effects. This is evident as in mouse models the deletion of COL3A1 resulted in aortic and gastrointestinal rupture meaning that simply restoring one functional copy may not be sufficient to prevent the disease. Moreover, the unknown and partial success in identifying mutations responsible for all EDS cases has further bolstered the struggle for researchers to establish comprehensive treatment strategies. In vEDS, as it is a dominantly inherited disorder, adding a healthy copy of the gene (a common strategy in gene therapy) is ineffective because the defective gene still produces harmful proteins. Research has highlighted, however, that the combination of RNAi-mediated mutant allele-specific gene silencing and transcriptional activation of a normal allele could help as a promising strategy for vascular Ehlers-Danlos Syndrome. In the experiment, researchers used small interfering RNA (siRNA) to selectively reduce the mutant COL3A1 mRNA levels by up to 80%, while simultaneously using lysyl oxidase (LOX) to boost the expression of the normal COL3A1 gene. This dual approach successfully increased the levels of functional COL3A1 mRNA in patient cells, suggesting a potential therapeutic strategy for this condition. Conclusion In conclusion, EDS represents a diverse group of inherited connective tissue disorders, primarily caused by mutations in collagen or collagen-modifying proteins. These genetic defects result in a wide range of symptoms, including joint hypermobility, skin hyperextensibility, and vascular complications, which vary significantly across the 13 different types of EDS. Diagnosing and treating EDS is complex and largely dependent on the specific genetic mutations involved. While current treatments mainly focus on managing symptoms and preventing complications, advances in genetic research, such as RNAi-mediated gene silencing and transcriptional activation, show promise for more targeted therapies, especially for severe forms like vascular EDS. However, challenges remain in developing comprehensive and effective treatments, underscoring the need for ongoing research and personalised medical approaches to improve the quality of life for individuals with EDS. Written by Imron Shah Related articles: Hypermobility spectrum disorders / Therapy for skin disease REFERENCES Malfait, F., Wenstrup, R.J. and De Paepe, A. (2010). Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genetics in Medicine, 12(10), pp.597–605. doi: https://doi.org/10.1097/gim.0b013e3181eed412 . Miklovic, T. and Sieg, V.C. (2023). Ehlers Danlos Syndrome. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK549814/ . Sobey, G. (2014). Ehlers–Danlos syndrome – a commonly misunderstood group of conditions. Clinical Medicine, [online] 14(4), pp.432–436. doi: https://doi.org/10.7861/clinmedicine.14-4-432 . Watanabe, A., Wada, T., Tei, K., Hata, R., Fukushima, Y. and Shimada, T. (2005). 618. A Novel Gene Therapy Strategy for Vascular Ehlers-Danlos Syndrome by the Combination with RNAi Mediated Inhibition of a Mutant Allele and Transcriptional Activation of a Normal Allele. Molecular Therapy, [online] 11, p.S240. doi: https://doi.org/10.1016/j.ymthe.2005.07.158 . FURTHER READING The Ehlers-Danlos Society - A global organisation dedicated to supporting individuals with EDS and raising awareness about the condition by providing extensive information on the different types of EDS, updates on research, and resources for patients https://www.ehlers-danlos.com/ PubMed - For those interested in academic research, articles and studies on EDS. https://www.ncbi.nlm.nih.gov/pmc/?term=ehlers-danlos+syndrome Cleveland Clinic – A clinic with an extensive health library providing easy to understand and informative information about the syndrome. https://my.clevelandclinic.org/health/diseases/17813-ehlers-danlos-syndrome Project Gallery

...In the nerve fibre world Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Squids are size champions 11/07/25, 09:53 Last updated: Published: 29/06/23, 09:33 ...In the nerve fibre world A cephalopod adventure When you think of squids, you probably imagine them swimming through the ocean and using tentacles to catch their prey. Scientists might not! These slimy sea creatures have helped us to study and understand how our own nervous system works. That’s right, squids are more than just tasty seafood. Squids have a giant axon, which is a single nerve fiber that is much larger than the axons found in other animals, including humans. This giant axon can be up to one millimeter in diameter , which is big enough to be seen with the naked eye. If you’re thinking that 1 millimeter is still pretty small, consider that human axons are measured in micrometers (µm) , so the squid’s giant axons are almost one thousand times larger in diameter than ours . In case you’re wondering what an axon is, it’s the long projection of a neuron that conducts electrical impulses away from the cell body. The electrical impulses generated during an action potential travel down the axon and make their way to the synapse. So the axon is a vital component of the nervous system that helps facilitate communication between neurons and other cells. In 1963, the English scientists Hodgkin and Huxley were awarded the Nobel Prize for their groundbreaking experiments on squid giant axons. Through their work, they provided a detailed understanding of the electrical properties of axon membranes and the role of ion channels in generating and propagating nerve impulses. They also discovered that the giant axon is surrounded by a thick layer of insulation called myelin , which speeds up the transmission of nerve impulses. Their research has been fundamental to the development of modern neurophysiology. So, the next time you enjoy a plate of calamari, remember that the squid on your plate might have contributed to our understanding of the nervous system. Written by Viviana Greco Related article: Frog nerves Project Gallery

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