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Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link From botulism to beauty: the evolution of botulinum toxins and botox 05/02/25, 16:31 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

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Herpes vs devastating skin disease 09/01/25, 12:07 Last updated: Published: 06/01/24, 11:14 From foe to ally Have you ever plucked loose skin near your nail, ripping off a tiny strip of good skin too? Albeit very small, that wound can be painful. Now imagine that it is not just a little strip that peels off, but an entire sheet. And it does not detach only when pulled, but at the slightest touch. Even a hug opens wounds, even a caress brings you pain. This is life with recessive dystrophic epidermolysis bullosa (RDEB), the most severe form of dystrophic pidermolysis bullosa (DEB). Herpes becomes a therapy DEB is a rare genetic disease of the skin that affects 3 to 10 individuals per million people (prevalence is hard to nail down for rare diseases). A cure is still far off, but there is good news for patients. Last May, the US FDA (Food and Drug Administration) approved Vyjuvek (beremagen geperparvec) to treat skin wounds in DEB. Clinical studies showed that it speeds up healing and reduces pain. Vyjuvek is the first gene therapy for DEB. It is manufactured by Krystal Biotech and - get this- it is a tweaked version of the herpes virus. Yes, you got that right, the virus causing blisters and scabs has become the primary ally against a devastating skin disease. This approval is a milestone for gene therapies, as Vyjuvek is the first gene therapy - based on the herpes virus, - to apply on the skin as a gel, - approved for repeated use. This article describes how DEB, and especially RDEB, affects the skin and wreaks havoc on the body; the following article will explain how Vyjuvek works. DEB disrupts skin integrity We carry around six to nine pounds of skin. Yet we often forget its importance: it stops germs and UVs, softens blows, regulates body temperature and makes us sensitive to touch. Diseases that compromise the skin are therefore devastating. These essential functions rely on the organisation of the skin in three layers: epidermis, dermis and hypodermis ( Figure 1 ). Typically, a Velcro strap of the protein collagen VII firmly anchors the epidermis to the dermis. The gene COL7A1 contains the instructions on how to produce collagen VII. In DEB, mutations in COL7A1 result in the production of a faulty collagen VII. As the Velcro strap is weakened, the epidermis becomes loosely attached to the dermis. Mutations in one copy of COL7A1 cause the dominant form of the disease (DDEB), mutations in both copies cause RDEB. With one copy of the gene still functional, the skin still produces some collagen VII, when both copies are mutated, little to no collagen VII is left. Therefore, RDEB is more severe than DDEB. In people with RDEB, the skin can slide off at the slightest touch and even gentle rubs can cause blisters and tears ( Figure 2 ). Living with RDEB Life with RDEB is gruelling and life expectancy doesn't exceed 30 years old. Wounds are very painful, slow to heal and get infected easily. The risk of developing an aggressive skin cancer is higher. The constant scarring can cause limb deformities. In addition, blisters can appear in the mouth, oesophagus, eyes and other organs. There is no cure for DEB for now; treatments can only improve the quality of life. Careful dressing of wounds promotes healing and prevents infections. Painkillers are used to ease pain. Special diets are required. And, to no one's surprise, physical activities must be avoided. Treating RDEB Over the past decade, cell and genetic engineering advances have sparked the search for a cure. Scientists have explored two main alternatives to restore the production of collagen VII in the skin. The first approach is based on transferring skin cells able to produce collagen VII. Despite promising results, this approach treats only tinyl patches of skin, requires treatments in highly specialised centres and it may cause cancer. The second approach is the one Vyjuvek followed. Scientists place the genetic information to make collagen VII in a modified virus and apply it to a wound. There, the virus infects skin cells, providing them with a new COL7A1 gene to use. These cells now produce a functional collagen VII and can patch the damage up. We already know which approach came up on top. Vyjuvek speeds up the healing of wounds as big as a smartphone. Professionals can apply it in hospitals, clinics or even at the patient’s home. And it uses a technology that does not cause cancer. But how does Vyjuvek work? And why did scientists choose the herpes virus to build Vyjuvek? We will find the answer in the following article. And since perfection does not belong to biology, we will also discuss the limitations of this remarkable gene therapy. NOTES: 1. DEB is part of a group of four inherited conditions, collectively named epidermolysis bullosa (EB), where the skin loses integrity. EB is also known as “Butterfly syndrome” because the skin becomes as fragile as a butterfly’s wing. These conditions are EB simplex, junction EB, dystrophic EB and Kindler EB. 2. Most gene therapies are based on modified, or recombinant in science jargon, adenoassociated viruses, which I reviewed for Scientia News. 3. Over 700 mutations have been reported. They disrupt collagen VII and its function with various degrees of severity. Consequently, RDEB and DDEB display several clinical phenotypes. 4. Two studies have adopted this approach: in the first study, Siprashvili and colleagues (2016) grafted ex vivo retrovirally-modified keratinocytes, the main cell type in the epidermis, over the skin of people with RDEB; in the second study, Lwin and colleagues (2019) injected ex vivo lentivirally-modified fibroblasts in the dermis of people with RDEB. Written by Matteo Cortese, PhD Related article: Ehler-Danos syndrome Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Cancer on the Move 05/12/24, 12:18 Last updated: Published: 30/01/24, 19:57 How can patients with metastasised cancer be treated? Introducing and Defining Metastasis Around 90% of patients with cancer die due to their cancer spreading (metastasis). Despite its prevalence, many critical questions remain in the field of cancer research about how and why cancers metastasise. The metastatic cascade has three main steps: dissemination, dormancy, and colonisation. Most cells that disseminate die once they leave the primary tumour, thus, posing an evolutionary bottleneck. However, the few that survive will face another challenge of entering a foreign microenvironment. Those circulating tumour cells (CTCs) acquire a set of functional abilities through genetic alterations, enabling them to survive the hostile environment. CTCs can travel as single cells or as clusters. If they travel in clusters, CTCs can be coated with platelets, neutrophils, and other tumour-associated cells, protecting CTCs from immune surveillance. As these CTCs travel further, they are named disseminated tumour cells (DTCs). These cells are undetectable by clinical imaging and can enter a state of dormancy. The metastatic cascade represents ongoing cellular reprogramming and clonal selection of cancer cells that can withstand the hostile external environment. How does metastasis occur, and what properties allow these cancer cells to survive? How & Why Does Cancer Metastasise? The Epithelial-to-Mesenchymal Transition (EMT) is a theory that explains how cancer cells can metastasise. In this theory, tumour cells lose their epithelial cell-to-cell adhesion and gain mesenchymal migratory markers. Tumour cells that express a mixture of epithelial and mesenchymal properties were found to be the most effective in dissemination and colonisation to the secondary site. It is important to note that evidence for the EMT has been acquired predominantly in vitro , where additional in vivo research is necessary to confirm this phenomenon. Nevertheless, although EMT does not accurately address why cancers metastasise, it provides a framework for how a cancer cell develops the properties to metastasise. Many factors contribute to why cancers metastasise. For example, a lack of blood supply, which occurs when a cancer grows too large, causes the cells in the centre to lack access to the oxygen carried by red blood cells. Thus, to evade cell death, cancer cells detach from the primary tumour to regain access to oxygen and nutrients. In addition, cancer cells exhibit a high rate of glycolysis to supply sufficient energy for its uncontrollable proliferation. However, this generates lactic acid as a by-product, resulting in a low pH environment. This acidic pH environment stimulates cancer invasion and metastasis as cancer cells move away from this hostile environment to evade cell death once again, an effect referred to as the ‘Warburg Effect’. In Figure 2, you can see that multiple interplaying factors that contribute to metastasis. So, how can patients with metastasised cancer be treated? Current Treatments and Biggest Challenges? Depending on what stage the patient presents at and what cancer type, the treatment options differ. Figure 3 shows an example of these treatment plans. For early stages I and II, chemotherapy and targeted treatments are offered, and in specific cases, local surgery is done. These therapies are done to slow the growth of the cancer or lessen the side effects of treatments. An example of treating metastasised prostate cancer includes hormone therapy, as the cancer relies on the hormone testosterone to grow. Currently, cytotoxic chemotherapy remains the backbone of metastatic therapy. However, there are emerging immunotherapeutic treatments under trial. These aim to boost the ability of the immune system to detect and kill cancer cells. Hopefully, these new therapies may improve the prognosis of metastatic cancers when used in complement with conventional therapies, shining a new light into the therapeutic landscape of advanced cancers. Future Directions Recent developments have opened new avenues to discovering potential treatment targets for metastatic cancer. The first is to target the dormancy of DTCs, where the role of the immune system plays an important part. Neoadjuvant ICI (immune checkpoint inhibitor) studies are anticipated to provide insight into novel biomarkers and can eliminate micro-metastatic cancer cells. Also, using novel technology such as single-cell RNA sequencing reveals complex information about the plasticity of metastatic cancer cells, allowing researchers to understand how cancer cells adapt in stressful conditions. Finally, in vivo models, such as patient-derived models, could provide crucial insight into future treatments as they reproduce the patients’ reactions to different drug treatments. There are many limitations and challenges to the research and treatment of cancer metastasis. It is clear, however, that with more studies into the properties of metastatic cancers and the different avenues of novel targets and therapeutics, there is a promising outcome in the field of cancer research. Written by Saharla Wasame Related articles: Epitheliod hemangioendothelioma / Immune signals and metastasis REFERENCES Fares, J., Fares, M.Y., Khachfe, H.H., Salhab, H.A. and Fares, Y. (2020). Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy , 5(1). doi: https://doi.org/10.1038/s41392-020-0134-x . Ganesh, K. and Massagué, J. (2021). Targeting metastatic cancer. Nature Medicine , 27(1), pp.34–44. doi: https://doi.org/10.1038/s41591-020-01195-4 . Gerstberger, S., Jiang, Q. and Ganesh, K. (2023). Metastasis. Cell , [online] 186(8), pp.1564–1579. doi: https://doi.org/10.1016/j.cell.2023.03.003 . Li, Y. and Laterra, J. (2012). Cancer Stem Cells: Distinct Entities or Dynamically Regulated Phenotypes? Cancer Research , [online] 72(3), pp.576–580. doi: https://doi.org/10.1158/0008-5472.CAN-11-3070 . Liberti, M.V. and Locasale, J.W. (2016). The Warburg Effect: How Does it Benefit Cancer Cells? Trends in Biochemical Sciences , [online] 41(3), pp.211–218. doi: https://doi.org/10.1016/j.tibs.2015.12.001 . Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H.K., Obenauf, A.C., Tosolini, M., Church, S.E., Maby, P., Vasaturo, A., Angelova, M., Fredriksen, T., Mauger, S., Waldner, M., Berger, A., Speicher, M.R., Pagès, F., Valge-Archer, V. and Galon, J. (2016). The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Science Translational Medicine , 8(327). doi: https://doi.org/10.1126/scitranslmed.aad6352 . Oscar Hernandez Dominguez, Yilmaz, S. and Steele, S.R. (2023). Stage IV Colorectal Cancer Management and Treatment. Journal of Clinical Medicine , 12(5), pp.2072–2072. doi: https://doi.org/10.3390/jcm12052072 . Steeg, P.S. (2006). Tumor metastasis: mechanistic insights and clinical challenges. Nature Medicine , [online] 12(8), pp.895–904. doi: https://doi.org/10.1038/nm1469 . Tarin, D. (2005). The Fallacy of Epithelial Mesenchymal Transition in Neoplasia. Cancer Research , 65(14), pp.5996–6001. doi: https://doi.org/10.1158/0008-5472.can-05-0699 . WANG, R.-A., LU, Y.-Y. and FAN, D.-M. (2015). Reasons for cancer metastasis: A holistic perspective. Molecular and Clinical Oncology , 3(6), pp.1199–1202. doi: https://doi.org/10.3892/mco.2015.623 . Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Anticancer Metal Compounds 28/01/25, 15:02 Last updated: Published: 23/05/23, 08:17 How metal compounds can be used as anti-cancer agents Metal compounds such as platinum, cobalt and ruthenium are used as anticancer agents. Anticancer metal compound research is important as chemotherapy is not selective, being very toxic to patients damaging normal DNA cells. Such metal compounds act as anti-cancer agents with the metals being able to vary in oxidation states. Selectivity of metal compounds to target only cancer cells arises from the metals properties of varying oxidation states for redox reactions. As cancer exists in hypoxic environments, the oxidation state of the metal is able to vary releasing the cancer drug only in the cancer environment. For example prodrugs are relatively inert metal complexes with relatively high oxidation states. PtIV, and CoIII are selective carriers undergoing reduction by varying the metals oxidation state in cancerous hypoxic environments releasing anticancer drugs. CoIII reduced to CoII, PtIV reduced to PtII in hypoxic environments. CoIII two oxidation states: Cobalt (III) is kinetically inert with low-spin 3d6 configuration, CoII is labile (high-spin 3d7). When CoIII is reduced to CoII in hypoxic environments, the active molecule is released then restored to its active form killing cancer cells. Cobalt can also bind to ligands like nitrogen mustards and curcumin ligands, exhibiting redox reactivity for cancer therapy. Nitrogen mustards are highly toxic due to their DNA alkylation and cross-linking activity. In vivo they are not selective for tumour tissue however can be deactivated by coordination to CoIII, released on reduction to CoII in hypoxic tumour tissue. This reduces systemic toxicity concluding an efficient anticancer drug. Platinum anticancer metal compounds treat ovarian, cervical and neck cancer. Platinum ( Pt IV) (cisplatin) exhibits redox-mediated anticancer activity, highly effective towards tumours. Platinum causes severe side-effects for patients so PtIV prodrug is used selectively reducing tumour sites. Ruthenium is used for cancer therapy as a less toxic metal over platinum. Ruthenium targeted therapy selectively disrupts specific cellular pathways where cancer cells rely for growth and metastasis. Reduction of Ru (III) to Ru(II) selectively occurs in hypoxic reducing environments where tumours over express transferrin receptors, ruthenium binding to. Overall metal compounds for cancer treatment attracted high interest due to redox activity properties. Metal compounds are selective to cancer cells, limiting patients' side effects. Such therapy shows how inorganic chemistry is important to medicine. Written by Alice Davey Related article: MOFs in cancer drug delivery Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The future of semiconductor manufacturing 13/12/24, 12:10 Last updated: Published: 22/12/23, 15:11 Through photonic integration Recently the researchers from the University of Sydney developed a compact photonic semiconductor chip by heterogeneous material integration methods which integrates an active electro-optic (E-O) modulator and photodetectors in a single chip. The chip functions as a photonic circuit (PIC) offering a 15 gigahertz of tunable frequencies with a spectral resolution of only 37 MHz and is able to expand the radio frequency bandwidth (RF) to precisely control the information flowing within the chip with the help of advanced photonic filter controls. The application of this technology extends to various fields: • Advanced Radar: The chip's expanded radio-frequency bandwidth could significantly enhance the precision and capabilities of radar systems. • Satellite Systems: Improved radio-frequency performance would contribute to more efficient communication and data transmission in satellite systems. • Wireless Networks: The chip has the potential to advance the speed and efficiency of wireless communication networks. • 6G and 7G Telecommunications: This technology may play a crucial role in the development of future generations of telecommunications networks. Microwave Photonics (MWP) is a field that combines microwave and optical technologies to provide enhanced functionalities and capabilities. It involves the generation, processing, and distribution of microwave signals using photonic techniques. An MWP filter is a component used in microwave photonics systems to selectively filter or manipulate certain microwave frequencies using photonic methods (see Figure 1 ). These filters leverage the unique properties of light and its interaction with different materials to achieve filtering effects in the microwave domain. They can be crucial in applications where precise control and manipulation of microwave signals are required. MWP filters can take various forms, including fiber-based filters, photonic crystal filters and integrated optical filters. These filters are designed to perform functions such as wavelength filtering, frequency selection and signal conditioning in the microwave frequency range. They play a key role in improving the performance and efficiency of microwave photonics systems. The MWP filter operates through a sophisticated integration of optical and microwave technologies as depicted in the diagram. Beginning with a laser as the optical carrier, the photonic signal is then directed to a modulator where it interacts with an input Radio-Frequency (RF) signal. The modulator dynamically influences the optical carrier's intensity, phase or frequency based on the RF input. Subsequently, the modulated signal undergoes processing to shape its spectral characteristics in a manner dictated by a dedicated processor. This shaping is pivotal for achieving the desired filtering effect. The processed optical signal is then fed into a photodiode for conversion back into an electrical signal. This conversion is based on the variations induced by the modulator on the optical carrier. The final output which is represented by the electrical signal reflects the filtered and manipulated RF signal which demonstrates the MWP's ability in leveraging both optical and microwave domains for precise and high-performance signal processing applications. Extensive research has been conducted in the field of MWP chips, as evidenced by a thorough examination in Table 1 . This table compares recent studies based on chip material type, filter type, on-chip component integration, and working bandwidth. Notably, previous studies demonstrated noteworthy advancements in chip research despite the dependence on external components. What distinguishes the new chip is its revolutionary integration of all components into a singular chip which is a significant breakthrough that sets it apart from previous attempts in the field. Here the term "On-chip E-O" involve the integration of electro-optical components directly onto a semiconductor chip or substrate. This integration facilitates the interaction between electrical signals (electronic) and optical signals (light) within the same chip. The purpose is to enable the manipulation, modulation or processing of optical signals using electrical signals typically in the form of voltage or current control. Key components of on-chip electro-optical capabilities include: 1. Modulators which alter the characteristics of an optical signal in response to electrical input which is crucial for encoding information onto optical signals. 2. Photonic detectors convert optical signals back into electrical signals extracting information for electronic processing. 3. Waveguides guide and manipulate the propagation of light waves within the chip, routing optical signals to various components. 4. Switches routes or redirects the optical signals based on electrical control signals. This integration enhances compactness, energy efficiency, and performance in applications such as communication systems and optical signal processing. "FSR-free operation" refers to Free Spectral Range (FSR) which is a characteristic of optical filters and resonators. FSR is the separation in frequency between two consecutive resonant frequencies or transmission peaks. The column "FSR-free operation" indicates whether the optical processing platform operates without relying on a specific or fixed Free Spectral Range. It means that its operation is not bound or dependent on a particular FSR. This could be advantageous in scenarios where flexibility in the spectral range or the ability to operate over a range of frequencies without being constrained by a specific FSR is desired. "On-chip MWP link improvement" refers to enhancements made directly on a semiconductor chip to optimize the performance of MWP links. These improvements aim to enhance the integration and efficiency of communication or signal processing links that involve both microwave and optical signals. The term implies advancements in key aspects such as data transfer rates, signal fidelity and overall link performance. On-chip integration brings advantages such as compactness and reduced power consumption. The manufacturing of the photonic integrated circuit (PIC) involves partnering with semiconductor foundries overseas to produce the foundational chip wafer. This new chip technology will play a crucial role in advancing independent manufacturing capabilities. Embracing this type of chip architecture enables a nation to nurture the growth of its autonomous chip manufacturing sector by mitigating reliance on international foundries. The extensive chip delays witnessed during the 2020 COVID pandemic underscored the global realization of the chip market's significance and its potential impact on electronic manufacturing. Written by Arun Sreeraj Related articles: Advancements in semi-conductor technology / The search for a room-temperature superconductor / Silicon hydrogel lenses Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Conservation of marine iguanas 17/10/24, 11:41 Last updated: Published: 06/01/24, 10:40 They are on the IUCN red list as 'vulnerable' The marine iguana ( Amblyrhynchus cristatus ), also known as the sea iguana, is a unique species. It is the world’s only ocean- going lizard. Their main food source is algae; large males can dive to forage for this source, while females feed during low tide. They can be found on rocky shorelines, but also on marshes, mangrove swamps and beaches of the Galapagos. Their range is limited to the Galapagos islands, so they are an isolated species. Currently, they are on the IUCN red list as ‘vulnerable’ with a current population estimated at 200,000, and conservation efforts are needed to stabilise populations. Key threats There are three key threats to iguana populations. The first is invasive species; animals such as pigs, dogs and cats feed on young hatchlings and iguana eggs, which reduces the long-term survival rate of the species. Marine iguanas have not yet developed defence strategies against these predators. Even humans introduce pathogens to the islands that pose a threat to the species, because of their isolated habitat, the marine iguana lacks immunity to many pathogens and so has a higher risk of contracting diseases. Climate change is another key threat. El Niño is a weather event that prevents cold, nutrient-rich waters, that the marine wildlife depends on, from reaching the Eastern Tropical Pacific. This depletes algae populations, and this food drop drastically reduces iguana populations ( Figure 1 ). With global warming, El Niño events are expected to be more prominent and more frequent. In addition, pollution from humans like oil spills and microplastics are damaging their habitat. Current and future conservation methods Under the laws of Ecuador, marine iguanas are completely protected. Their land range is in the Galapagos National Park, and their sea range is within the Galapagos Marine Reserve. They are also listed on the CITES, which ensures monitoring the trade of endangered animals to inhibit damage to their numbers. Sanctuaries are also in place to mitigate against extinction, but their specialised diet is challenging. So, what does the future hold for marine iguanas? The biggest challenge is the distribution of the species. The population is scattered across the different islands of the Galapagos as such, there are at least 11 subspecies. This brings more complications to marine iguana conservation. As these subspecies specialise, it becomes less likely they will breed, thus more difficult to maintain the species population. Introducing education and awareness programmes will better equip us to the dangers faced by marine iguanas and could be a tourism idea for the Galapagos. This species is one of a kind, which is why it is so important for them to be protected.There should be a monitoring scheme, as suggested by MacLeod and Steinfartz, 2016 ( Figure 2 ), but the location of these subspecies makes it difficult to monitor them. However, there was a recent study using drone-based methods which showed promising results ( Figure 3 ). The overarching question remains: do we continue to conserve the current population in the Galapagos, or should we relocate the species to a less endangered habitat. Written by Antonio Rodrigues Related articles: Conservation of Galapagos Tortoises / 55 years of vicuna conservation Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The science and controversy of water fluoridation 17/02/25, 14:49 Last updated: Published: 17/11/23, 17:00 Diving deep In the pursuit of national strategies to improve oral health, few interventions have sparked as much debate and divided opinions as water fluoridation. Whilst some have voiced concerns about water fluoridation in recent years, viewing it as mass medicalisation and an intrusion into personal choice, researchers and dental professionals continue to champion its benefits as a cost-effective, population-wide approach that can significantly reduce tooth decay and enhance the oral health of communities across the country. The statistics from 2021-2022 paint a concerning picture, with a staggering 26,741 extractions performed on 0-19-year-olds under the NHS due to preventable tooth decay, amounting to an estimated cost of £50 million. With the NHS bearing the responsibility of providing dental care to millions of people nationwide, the introduction of water fluoridation stands out as a promising ally in the quest for more efficient healthcare and the alleviation of the burden on our already-strained healthcare system, all while improving dental health in a cost-effective manner. Fluoride is a naturally occurring chemical element found in soil, plants and groundwater, which can reduce dental decay through a dual mechanism; fluoridating water reduces dental decay by both impeding demineralisation of enamel and enhancing remineralisation of teeth following acid attacks in the mouth. When sugars from food or drinks enter the mouth, the bacteria present in plaque act to convert these sugars to acid, demineralising the outer surface of teeth and leading to the formation of cavities. The incorporation of fluoride into the structure of tooth enamel during remineralisation strengthens and hardens the outer layer of teeth, rendering teeth less susceptible to damage and more resistant to acid-induced demineralisation. Moreover, fluoride has also been proven to reverse early tooth decay by repairing and remineralising weakened enamel, thus averting the need for restorative dental procedures such as fillings. The inhibition of demineralisation and encouragement of remineralisation overall prevents cavities forming and preserves the vitality of our smiles. The main adverse effect of fluoridating water is the risk of dental fluorosis, which affects the appearance of teeth. Dental fluorosis is a cosmetic dental condition caused by excessive fluoride exposure, resulting in changes in tooth colour and texture. It presents as small opaque white spots or streaks on the tooth surface. It is important to note that these conditions generally occur at fluoride levels significantly higher than those recommended for water fluoridation. Opponents of water fluoridation also argue on ethical grounds, citing concerns about mass medication infringing on personal choice and the right to decide whether to use fluoride or dental products containing fluoride. In some cases, opposition is rooted in conspiracy theories and scepticism about government motives. Findings from the Office for Health Improvement and Disparities and the UK Health Security Agency highlight the benefits of water fluoridation. The data collected illustrates young populations in areas of England with higher fluoride concentrations are up to 63% less likely to be admitted to hospital for tooth extractions due to decay compared to their counterparts in areas of lower fluoridation levels. This disparity is most pronounced in the most deprived areas, where children and young adults benefit the most from the addition of fluoride to the water supply. These findings strongly support the evidence for the advantages of water fluoridation and highlight how this simple method can substantially improve health outcomes for our population. While fluoridation has proven beneficial for communities, especially those from deprived backgrounds, it has demonstrated successful outcomes for individuals across all demographics, irrespective of age, education, employment, or oral hygiene habits. It's essential to emphasize that water fluoridation should not replace other essential oral health practices such as regular tooth brushing, prudent sugar intake, and dental appointments. Instead, it should complement these practices, working in synergy to optimize oral health. As of now, approximately 10% of the population in England receives water from a fluoridation scheme. While the protective and beneficial effects of fluoridation are well-established, the decision to move towards a nationwide water fluoridation scheme ultimately rests with the Secretary of State for Health in the coming years. Written by Isha Parmar Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Brain-Climate Connection: The Hidden Impact of Rising Temperatures 19/11/24, 17:38 Last updated: Published: 24/05/23, 09:55 Rising temperatures can affect brain health Global warming is not only disrupting ecosystems, affecting the food we eat and the air we breathe, but it’s also impacting our neurological health. According to the 2022 Global Climate Report from NOAA National Centers for Environmental Information , 2022 was the sixth warmest year since 1880. To understand this better, let’s start with the basics. The brain is made up of billions of tiny cells called neurons that communicate with each other by generating electrochemical signals. Think of neurons as small batteries capable of producing electricity when triggered by electrically charged chemicals, called ions. When a neuron is at rest, so when it’s not transmitting an electrical signal, it maintains a negative charge inside compared to the outside. This difference in charge is created by the selective movement of ions across the neuron’s membrane through ion channels and pumps. The resting membrane potential of a neuron is typically around -70 millivolts (mV). When a neuron needs to send information, it generates electrical activity called action potential , which causes the electrical charge to become less negative and closer to zero. To trigger a full-sized action potential, the electrical charge needs to reach a threshold of approximately -55 mV. If the charge reaches this threshold, a full-sized action potential is triggered and the neuron will send a signal down to other neurons. However, If the electrical charge does not reach this threshold, the neuron will not send a signal at all. This is known as the “ALL OR NONE” principle. The action potential is a crucial part of the neuron’s communication process, as it allows the neuron to send signals quickly and efficiently to other neurons. But here’s the catch: temperature fluctuations can affect the ion channels that generate and propagate action potentials, which are critical for the neuron’s communication process. It turns out that an increase in temperature can influence the generation , speed , and duration of action potentials. But that’s not all! Hotter temperatures can trigger seizures in individuals with epilepsy or a history of seizures. One of the most concerning findings from scientific research is that climate change, among other factors, may contribute to an increase in seizure severity and frequency, as well as the development of cerebrovascular and neurodegenerative diseases, such as strokes or dementia . Triggering stress and sleep deprivation, heat waves can also exacerbate the symptoms of such pre-existing disorders. The good news is that we can take action to address the direct impact of climate change on our planet and health. Joining initiatives like Climatematch Academy (CMA) , a 2-week interactive online summer school, can help you learn more about climate science and become part of a global community that is working towards a more sustainable future. CMA is an all-volunteer organization run by dozens of science enthusiasts. It aims at introducing computational methods for climate science taking advantage of available open-source tools and datasets to make science accessible to students worldwide. This is your chance to learn cutting-edge techniques from climate science experts and make a difference in the world, ensuring a brighter future for ourselves and future generations. Written by Viviana Greco Related article: The environmental impact of EVs Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Why is there a need for cardiac regeneration? Last updated: 13/03/25, 11:37 Published: 06/03/25, 08:00 Restoring cardiac tissue and reducing heart failure Cardiovascular disease (CVD) remains a predominant cause of morbidity and mortality on a global scale. Among its various manifestations, heart failure (HF) stands out as a significant public health concern, with a prevalence exceeding 23 million individuals worldwide. Heart failure, especially after a heart attack (myocardial infarction) or ischemic heart disease, is a major challenge. The five-year survival rate is less than 50%. In these patients, functional cardiomyocytes are substantially lost (cardiomyocytes refer to cardiac muscle cells). The remaining cardiomyocytes often attempt to compensate for this loss; however, this compensatory mechanism can lead to scar tissue formation, subsequently compromising the overall functionality of the cardiac muscle. Despite numerous advancements in medical science and therapeutic interventions, restoring lost cardiomyocytes in the adult mammalian heart remains a significant obstacle due to its poor regenerative capacity. Consequently, there exists an urgent need for novel therapeutic approaches. Cardiac regeneration has emerged as a promising field of research focused on restoring cardiac tissue and reducing heart failure, offering hope for improved clinical outcomes in affected patients. Approaches for cardiac regeneration Cardiac regeneration has emerged as a pivotal area of research, and various innovative strategies, including stem cell therapies and gene therapy, are being explored. Stem cell therapies: Stem cell therapies utilise the ability of stem cells to differentiate into cardiomyocytes or release factors that promote tissue repair. Preclinical studies involving animal models and early-phase clinical trials have demonstrated that stem cell interventions can enhance cardiac function. However, significant challenges remain concerning the efficacy and safety of these therapies in human subjects, necessitating further investigation. Gene therapy: Gene therapy delivers specific genes that directly support cell proliferation, differentiation, and survival to damaged cardiac tissue. Introducing these genes can activate specific intracellular signalling pathways, resulting in the replication and maturation of cardiac muscle cells. Ultimately, this strategy aims to restore normal heart function and improve cardiac health. Benefits of cardiac regeneration Cardiac regeneration has the potential to significantly enhance survival rates and improve the quality of life for patients with heart conditions. Compared to heart transplantation, cardiac regeneration offers a less invasive alternative with fewer complications related to immune rejection and lifelong immunosuppressive therapy. Some of the potential benefits of cardiac regeneration are: Replacing the scar formation and improving heart function Reduce the dependency on medications Alternative to heart transplantation Reducing the healthcare costs Challenges to cardiac regeneration Cardiac regeneration remains a complex field marked by ethical considerations and scientific challenges that require thorough exploration. Stem cell therapy limitations include low engraftment rates, potential tumorigenesis, and difficulty effectively integrating host cardiac tissue. Additionally, immune rejection poses a substantial risk, affecting safety and efficacy. Beyond biological hurdles, the high cost of research, treatment development, and patient care presents a significant challenge to widespread adoption. Regulatory approval processes add another layer of complexity, as therapies must meet stringent safety and efficacy standards before clinical use. Furthermore, scalability remains an issue, as translating experimental techniques into large-scale, cost-effective treatments is a major obstacle in making cardiac regeneration accessible to a broader population. Moreover, it is imperative to deepen our understanding of the roles played by non-cardiomyocyte cell types such as endothelial cells, fibroblasts, and immune cells in cardiac regeneration. Conclusion Cardiac regeneration is a ray of hope for heart patients, significantly enhancing their chances of survival and quality of life. Therefore, cardiac regeneration demands thorough exploration, as it has the potential to transform the treatment and management of cardiovascular disease. Written by Prabha Rana Related article: Hypertension REFERENCES Baccouche, B. M., Elde, S., Wang, H., & Woo, Y. J. (2024). Structural, angiogenic, and immune responses influencing myocardial regeneration: a glimpse into the crucible. Npj Regenerative Medicine, 9(1), 18. https://doi.org/10.1038/s41536-024-00357-z Pezhouman, A., Nguyen, N. B., Kay, M., Kanjilal, B., Noshadi, I., & Ardehali, R. (2023). Cardiac regeneration - Past advancements, current challenges, and future directions. Journal of Molecular and Cellular Cardiology, 182, 75–85. https://doi.org/10.1016/j.yjmcc.2023.07.009 Sacco, A. M., Castaldo, C., di Meglio, F. di, Nurzynska, D., Palermi, S., Spera, R., Gnasso, R., Zinno, G., Romano, V., & Belviso, I. (2023). The Long and Winding Road to Cardiac Regeneration. Applied Sciences, 13(16), 9432. https://doi.org/10.3390/app13169432 van der Pol, A., & Bouten, C. V. C. (2021). A Brief History in Cardiac Regeneration, and How the Extra Cellular Matrix May Turn the Tide. Frontiers in Cardiovascular Medicine, 8. https://doi.org/10.3389/fcvm.2021.682342 Wang, J., An, M., Haubner, B. J., & Penninger, J. M. (2023). Cardiac regeneration: Options for repairing the injured heart. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.981982 Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Genetics of Ageing and Longevity 20/02/25, 11:55 Last updated: Published: 13/05/24, 15:20 A well-studied longevity gene is SIRT1 Ageing is a natural process inherent to all living organisms. Yet, its mechanisms remain somewhat enigmatic. While lifestyle factors undoubtedly influence longevity, recent advancements in genetic research have revealed the influence of our genomes on ageing. Through understanding these influences, we can unlock further knowledge on longevity, which can aid us in developing interventions to promote healthy ageing. This article delves into the world of ageing and longevity genetics and how we can use this understanding to our benefit. Longevity genes A number of longevity genes, such as APOE , FOXO3 , and CETP, have been identified. These genes influence various biological processes, including cellular repair, metabolism, and stress response mechanisms. A well-studied longevity gene is SIRT1 . Located on chromosome 10, SIRT1 encodes sirtuin 1, a histone deacetylase, transcription factor, and cofactor. Its roles include protecting cells against oxidative stress, regulating glucose and lipid metabolism, and promoting DNA repair and stability via deacetylation. Sirtuins are an evolutionarily conserved mediator of longevity in many organisms. One study looked at mice with knocked-out SIRT1 ; these mice had significantly lower lifespans when compared with WT mice1. The protective effects of SIRT1 are thought to be due to deacetylating p53, which promotes cell death2. SIRT1 also stimulates the cytoprotective and stress-resistance gene activator FoxO1A (see Figure 1 ), which upregulates catalase activity to prevent oxidative stress3. Genome-wide association studies (GWAS) have identified several genetic variants associated with ageing and age-related diseases. Such variants influence diverse aspects of ageing, such as cellular senescence, inflammation, and mitochondrial function. For example, certain polymorphisms in APOE are associated with an increased risk of age-related conditions like Alzheimer's and Parkinson’s disease4. These genes have a cumulative effect on the longevity of an organism. Epigenetics of ageing Epigenetic modifications, such as histone modifications and chromatin remodelling, regulate gene expression patterns without altering the DNA sequence. Studies have shown that epigenetic alterations accumulate with age and contribute to age-related changes in gene expression and cellular function. For example, DNA methylation is downregulated in human fibroblasts during ageing. Furthermore, ageing correlates with decreased nucleosome occupancy in human fibroblasts, thereby increasing the expression of genes unoccupied by nucleosomes. One specific marker of ageing in metazoans is H3K4me3, indicating the trimethylation of lysine 4 on histone 3; in fact, H3K4me3 demethylation extends lifespan. Similarly, H3K27me3 is also a marker of biological age. By using these markers as an epigenetic clock, we can predict biological age using molecular genetic techniques. As a rule of thumb, genome-wide hypomethylation and CpG island hypermethylation correlate with ageing, although this effect is tissue-specific5. Telomeres are regions of repetitive DNA at the terminal ends of linear chromosomes. Telomeres become shorter every time a cell divides (see Figure 2 ), and eventually, this can hinder their function of protecting the ends of chromosomes. As a result, cells have complex mechanisms in place to prevent telomere degradation. One of these is the enzyme telomerase, which maintains telomere length by adding G-rich DNA sequences. Another mechanism is the shelterin complex, which binds to ‘TTAGGG’ telomeric repeats to prevent degradation. Two major components of the shelterin complex are TRF1 and TRF2, which bind telomeric DNA. They are regulated by the chromatin remodelling enzyme BRM-SWI/SNF, which has been shown to be crucial in promoting genomic stability, preventing cell apoptosis, and maintaining telomeric integrity. BRM-SWI/SNF regulates TRF1/2, thereby, regulating the shelterin complex, by remodelling the TRF1/2 promoter region to convert it to euchromatin and increase transcription. BRM-SWI/SNF inactivating mutations have been shown to contribute to cancer and cellular ageing through telomere degradation6. Together, the mechanisms cells have in place to protect telomeres provide protection against cancer as well as cellular ageing. Future of anti-ageing drugs Anti-ageing drugs are big business in the biotechnology and cosmetics sector. For example, senolytics are compounds that decrease the number of senescent cells in an individual. Senescent cells are those that have permanently exited the cell cycle and now secrete pro-inflammatory molecules (see Figure 3); they are a major cause of cellular and organismal ageing. Senolytic drugs aim to provide anti-ageing benefits to an individual, whereby senescent cells are removed, therefore, decreasing inflammation. Currently, researchers are certain that removing senescent cells would have an anti-ageing effect, although senolytic drugs currently on the market are understudied, and so their side effects are unknown. Speculative drugs could include those that enhance telomerase or SIRT1 activity. Evidently, ageing is not purely determined by lifestyle and environmental factors alone but also by genetics. While longevity genes are hereditary, epigenetic modifications may be influenced by external factors. Therefore, we can attribute the complex interplay between various external factors and an individual’s genome to understanding the role of genetics in ageing. Perhaps we will see a new wave of anti-ageing treatments in the coming years, developed on the genetics of ageing. Written by Malintha Hewa Batage Related articles: An introduction to epigenetics / Schizophrenia, inflammation and ageing / Ageing and immunity REFERENCES Cilic, U et al., (2015) ‘A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human’, PLoS One , 10(3). Alcendor, R et al., (2004) ‘Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes’, Circulation Research , 95(10):971-80. Alcendor, R et al., (2007) ‘Sirt1 regulates aging and resistance to oxidative stress in the heart’, Circulation Research , 100(10):1512-21. Yin, Y & Wang, Z, (2018) ‘ApoE and Neurodegenerative Diseases in Aging’, Advances in Experimental Medicine and Biology , 1086:77-92. Wang, K et al., (2022) ‘Epigenetic regulation of aging: implications for interventions of aging and diseases’, Signal Transduction and Targeted Therapy , 7(1):374. Images made using BioRender. Project Gallery