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Can we extend lifespan in Drosophila by changing gene expression or by drug treatments?
Get PDFAging is a complex process involving physiological and functional changes in cellular activities, genetic pathways, and overall organismal integrity. The increasing global population and longer life expectancy have indeed created a growing urgency to find ways to extend health span. Considering health span not solely, life span is crucial to reduce the social and economic burden of aging populations. Number of years a person lives in good health free from any chronic disease and disability is more important that the total number of years he lived. A longer life accompanied by more years of chronic illness, frailty, and dependency leads to escalating medical expenses, long-term care needs, and increased public spending. This means not just adding years to life but adding healthy years is important. Studying gene expression is a powerful tool to understand aging. Ideally, aim of this study was to overexpress a specific gene at defined times within an organism. The GAL4 GeneSwitch system, a modified version of the UAS/GAL4 system, allows for such control over gene expression. It uses the drug RU486 to activate a modified GAL4 protein, enabling both spatial (tissue-specific) and temporal (time-controlled) gene regulation. This system can be used to manipulate genes potentially relevant to aging. In this study, GeneSwitch system was employed to investigate the effects of gene manipulation on lifespan and climbing speed in male fruit flies (Drosophila melanogaster). Glyceraldehyde-3-phosphate dehydrogenase (gapdh 1) is known for its role in glycolysis and is called moonlight protein because of its multifunctional activities as it acts as a transcription factor and influences cell survival and proliferation. It was used in this research because its expression decreases with age quite a lot, both sexes, and it’s expressed ubiquitously and fairly high levels (Flybase). In the first experiment, the Glyceraldehyde-3-phosphate dehydrogenase (gapdh) gene was overexpressed under the control of tissue-ubiquitously expressing promoters (Actin and daughterless). Although gapdh was not overexpressed significantly in the experiment. So, overall lifespan was not significantly extended, flies carrying only the UAS- gapdh transgene (without the GeneSwitch driver) did show a longer lifespan. Interestingly, flies with the GeneSwitch driver alone (ActinGS-255B) displayed increased activity compared to another fly strain (daughterless). The results showed no increase in lifespan of flies. These results highlighted the importance of further research into the gapdh gene and further explanation of its role in ageing. Anti-aging drug therapy is considered one of the most promising strategies to tackle the effects of ageing. Combination of different drugs can extend healthy life span when they target age-related mechanisms. In the second project, four different drugs (alagebrium, baicalein, lithium, bathophenanthroline disulfonic acid), individually and in combination were used to investigate their effect on the lifespan of two wildtype fly strains (Lancaster and Dahomey). 1) Alagebrium is known as cross link breaker formed by advanced glycation end products (AGEs) which are linked to aging. 2) Baicalein is a flavonoid with antioxidant, antibiotic, and free radical scavenging properties. 3) One of the most significant roles of lithium is inhibition of glycogen synthase kinase-3 (GSK-3) which is a tau protein kinase-1 which regulate tau phosphorylation in Alzheimer disease and reported to extend lifespan of Drosophila by inhibiting glycogen synthase kinase-3 (GSK-3) via activation of transcription factor nuclear factor erythroid 2 related factor (NRF-2). 4) Bathophenanthroline disulfonic acid (BPS) is an iron chelator that reduces lipid peroxidation, a damaging process in cells. The results showed no significant impact on lifespan for most drug combinations. However, a combination of three drugs (alagebrium, lithium, and baicalein) did lead to a slight increase (3%) the median lifespan of flies from the Dahomey strain (p=0.05). In wDah flies, lithium itself significantly increased the median life span of wDah flies by 3% and significantly extended the median lifespan of Lancaster flies by 6% to 67 days (P<0.05). The results suggest that these drugs and their combinations did not increase lifespan drastically and they are not worth pursuing, and that the papers using lithium overestimated its effects. As well as it will likely a step towards using novel drugs to extend healthy life span in future
The Role of the Invasion of Afghanistan and Reputation in President Carter's Handling of the Iran Hostage Crisis : Prioritizing International Over Domestic Factors
No full textPresident Carter's handling of the Iran Hostage Crisis was an archetypal example of the influence of presidential personality and domestic factors on force preference decision-making. Carter's worldview allegedly led him to prioritize hostage safety and shun the use of force. However, this article presents a revisionist account of the crisis based on newly declassified documents that demonstrates that international factors, including the invasion of Afghanistan, the regional balance of power, and American credibility were determinative. Contrary to his reputation as a weak leader, Carter actively sought a military solution to the conflict, but his ability to act was constrained by the Soviet invasion of Afghanistan. Following the invasion, Carter's focus shifted from using force against Iran to deterring a Soviet invasion of the country. The article alters the current understanding of the crisis and challenges the dominance of personality and domestic factors in the use of force decision-making literature
Understanding catchment phosphorus pressures using an innovative monitoring system
No full textFreshwater phosphorus pollution is recognised as a cause for concern worldwide due to its relationship with eutrophication, and the first challenge faced is its monitoring. This is because the most common method for monitoring is infrequent (monthly) grab sampling – which is discrete both spatially and temporally. A lack of data makes identifying sources and incidents of phosphorus pollution difficult. Techniques capable of collecting spatial and temporal phosphorus data are therefore of interest to water stewards and researchers. DGT (diffusive gradients in thin-films) passive sampling is thought to be capable of meeting such needs. It is, by design, a time-weighted average sampler that can be easily deployed in multiple locations. However, there have been few field studies demonstrating the technique for phosphorus monitoring. This thesis therefore aimed to establish DGT as a reliable, scalable monitoring tool for the field measurement of phosphorus in rivers and catchment systems. Different deployment systems were investigated for impacts upon DGT measured concentrations. It was demonstrated that deployment system had no impact upon DGT measured concentration and therefore recommended that DGT samplers be deployed in whichever system best suits site conditions. After comparison with high-frequency data it was preliminarily demonstrated that DGT successfully monitor temporal changes in phosphorus concentrations, and that DGT measure labile phosphorus concentrations, which are lower than total reactive and soluble reactive fractions in most cases. Incidences of spatial and temporal phosphorus pollution were reported according to DGT sampling results and diffuse and point sources of phosphorus pollution were identified within catchments by the technique. Additionally, DGT effectively measured significant decreases in river phosphorus concentrations following the implementation of mitigation technologies in wastewater treatment plants/storm dilution. This thesis therefore preliminarily demonstrated DGT as a versatile monitoring tool capable of spatial and temporal catchment investigations, and for use in monitoring mitigation effectiveness and phosphorus pollution control
SceneLLM : Implicit language reasoning in LLM for dynamic scene graph generation
Get PDFDynamic scenes contain intricate spatio-temporal information, crucial for mobile robots, UAVs, and autonomous driving systems to make informed decisions. Parsing these scenes into semantic triplets Subject-Predicate-Object for accurate Scene Graph Generation (SGG) is highly challenging due to the fluctuating spatio-temporal complexity. Inspired by the reasoning capabilities of Large Language Models (LLMs), we propose SceneLLM, a novel framework that leverages LLMs as powerful scene analyzers for dynamic SGG. Our framework introduces a Video-to-Language (V2L) mapping module that transforms video frames into linguistic signals (scene tokens), making the input more comprehensible for LLMs. To better encode spatial information, we devise a Spatial Information Aggregation (SIA) scheme, inspired by the structure of Chinese characters, which encodes spatial data into tokens. Using Optimal Transport (OT), we generate an implicit language signal from the frame-level token sequence that captures the video's spatio-temporal information. To further improve the LLM's ability to process this implicit linguistic input, we apply Low-Rank Adaptation (LoRA) to fine-tune the model. Finally, we use a transformer-based SGG predictor to decode the LLM's reasoning and predict semantic triplets. Our method achieves state-of-the-art results on the Action Genome (AG) benchmark, and extensive experiments show the effectiveness of SceneLLM in understanding and generating accurate dynamic scene graphs
Degree Growth in Graded Cluster Algebras
Get PDFThis thesis focuses on graded cluster algebras, looking specifically at degree growth. We begin by considering the rank 3 skew-symmetric case, building on earlier work by Booker-Price. We establish the existence of fastest growing paths, and compare the behaviour for different initial conditions. The central part of the thesis concerns the cluster algebra structure on the homogeneous coordinate ring of the Grassmannian. We construct a distinguished mutation path with certain nice properties. In particular, we suggest a way of using this mutation path to define a partial order on cluster variables, making use of perfect matchings on the exchange quivers. We show that, at least in the finite type case, the partial order we obtain coincides with the ‘standard’ partial order which appears in work of Lenagan and Rigal on quantum graded algebras with a straightening law. We hope that the connection with Lenagan and Rigal’s work could be used to transfer the techniques they use in order to establish the homological properties of other classes of (quantum) cluster algebra. In the final part of the thesis we show that, under mild assumptions, the Segre product of two graded cluster algebras has a natural cluster structure
A Comprehensive Review on Strategic Allocation of Renewables and Electric Vehicle Infrastructure in Future Power Networks
No full textThe global shift towards cleaner energy and sustainable mobility, motivated by international climate commitments such as the Paris Agreement, has accelerated the adoption of electric vehicles (EVs) and renewable energy sources (RESs). In this chapter, a comprehensive review of the key challenges is presented, including enabling technologies and optimisation approaches involved in jointly deploying electric vehicle charging stations (EVCSs) and renewable generation within active distribution networks. Its novelty lies in presenting a framework that integrates technical, economic, environmental, and regulatory perspectives, while formulating a taxonomy that links energy management, optimisation, and policy aspects into a unified planning framework. The review identifies four main categories of barriers: technical, economic and infrastructural, environmental, and planning or regulatory. It also explores a variety of EV charging strategies, such as vehicle-to-grid, grid- to-vehicle (G2V), inductive wireless charging, battery swapping, and smart charging, to assess their influence on load profiles and grid stability. To enable reliable and flexible integration of EVCSs and RESs, advanced energy management frameworks are examined, including demand response strategies, aggregator-based distributed control, and hierarchical control architectures. Furthermore, the chapter highlights the importance of multi-objective optimisation in managing trade-offs among competing goals, such as cost efficiency, carbon reduction, voltage stability, and social acceptance. It reviews a range of decision-support tools for optimal siting, sizing, and operation of EVCS and RES infrastructure. Overall, this work provides a well-structured synthesis of current research and practical developments, offering valuable insights for policymakers, utilities, and researchers to inform future energy planning, investment decisions, and policy formulation
Crohn’s Disease in Malaysia : Could Application of the Precautionary Principle Reduce Future Incidence?
No full textInflammatory bowel disease (IBD) comprises mainly Crohn’s disease (CD) and Ulcerative Colitis (UC). The Western model suggests that environmental factors, immunological factors, the gut microbiome, and genetic disposition all contribute to the onset and sustained symptoms that define CD, although the pathogenesis of CD remains unresolved. Current studies propose that in individuals who are genetically susceptible, genetic factors linked to immune dysregulation, in combination with environmental exposure, can result in dysbiosis of the gut microbiome and intestinal barrier dysfunction, leading to immune dysregulation. In Malaysia, the incidence of IBD is rising with CD increasing disproportionally compared to UC, and the incidence of CD currently mirrors that of the United Kingdom in the 1930s, which now has one of the highest incidences worldwide. Given the suggested role of Mycobacterium avium subspecies paratuberculosis (MAP) in CD in Western countries, which is subject to some controversy, this review summarises for the first time the current evidence on genetic, environmental, and microbial factors that could contribute to the rise of Crohn’s disease in Malaysia and proposes preventive approaches. We note the increasing reliance of Malaysia on imported cattle and milk products from areas of high Johne’s Disease prevalence to meet increasing demand and changes in milk preferences in the Malaysian population, both key indicators for human-MAP exposure in the Western model. Therefore, should MAP be shown to be associated with CD in Malaysia, some preventative measures are suggested, such as screening imported and native beef and dairy cattle, dairy products and ultimately water, both recreational and potable
Immunobiology of the serous cavities
Get PDFThe serous cavities are fluid-filled spaces that surround the lung, heart, and abdomen. One of their main functions is to provide protection and lubrication for their encapsulated organs. In addition to these physiological roles, the serous cavities are rich immune cell reservoirs. Although these cavity-derived immune cells have been studied ex vivo for many years, the past decade has led to substantial advances in serous cavity biology. Importantly, immune mechanisms that occur in these fluid environments and communication networks between these cavities and the tissues that they contain have been elucidated. In this Review, we aim to summarize the current knowledge of cellular and molecular interactions that govern immunology across all serous cavities, comparing animal models and human studies. A deeper understanding of how the serous cavities provide immune protection to the tissues that they encompass is likely to reveal therapeutic avenues for manipulation of these cavities to improve disease outcomes
Fishing-focused marine conservation planning underestimates losses of other ecosystem benefits to local communities
No full textIncorporating meaningful social and economic information into conservation planning is challenging but critical to minimizing impacts of conservation actions on livelihoods and increasing the likelihood of compliance with restrictions on resource use. The social impacts of conservation reserves are generally included in planning mostly through opportunity costs. For marine systems, these opportunity costs tend to be measured only for fishers. However, the services and associated benefits people gain from their marine environments go beyond food and income from fishing. People also benefit from recreation, aesthetic enjoyment, spiritual connections, medicine, and culture. We explored how conservation planning can be informed and optimized with data on how people value coral-reef ecosystem benefits. We identified and mapped important places, including for fishing, to households of the Riwo (Ziwo) community of the Madang Lagoon, Papua New Guinea, using interviews from heads of households (n = 52). Then, we incorporated data on the multiple benefits of the Madang Lagoon into spatial prioritization with novel cost functions. We found that different places in the Madang Lagoon were important for different reasons, and that designing reserves only to minimise forgone fishing can have incidental impacts on other benefits. We also found that incorporating information on all benefits was the most effective way to minimize the loss of the full suite of benefits, should their access be limited by reserves. We demonstrated how planners can develop approaches that consider all the various costs of conservation that matter to local people