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39 result(s) for "Dhakal, Subash"
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TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells
Understanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Previously, we demonstrated the role of TRPγ in nutrient-sensing behavior (Dhakal et al., 2022). Here, we found that a TRPγ mutant exhibited in Drosophila melanogaster is required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) of D. melanogaster . Interestingly, trpγ deficient mutants exhibited elevated TAG levels and our genetic data indicated that Dh44 neurons are indispensable for normal lipid storage but not protein storage. The trpγ mutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated that trpγ knockout downregulated brummer , a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulate nutrient storage.
A single pair of pharyngeal neurons functions as a commander to reject high salt in Drosophila melanogaster
Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster , internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b , is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.
Drosophila TRPγ is required in neuroendocrine cells for post-ingestive food selection
The mechanism through which the brain senses the metabolic state, enabling an animal to regulate food consumption, and discriminate between nutritional and non-nutritional foods is a fundamental question. Flies choose the sweeter non-nutritive sugar, L-glucose, over the nutritive D-glucose if they are not starved. However, under starvation conditions, they switch their preference to D-glucose, and this occurs independent of peripheral taste neurons. Here, we found that eliminating the TRPγ channel impairs the ability of starved flies to choose D-glucose. This food selection depends on trpγ expression in neurosecretory cells in the brain that express diuretic hormone 44 (DH44). Loss of trpγ increases feeding, alters the physiology of the crop, which is the fly stomach equivalent, and decreases intracellular sugars and glycogen levels. Moreover, survival of starved trpγ flies is reduced. Expression of trpγ in DH44 neurons reverses these deficits. These results highlight roles for TRPγ in coordinating feeding with the metabolic state through expression in DH44 neuroendocrine cells.
Ionotropic receptors mediate nitrogenous waste avoidance in Drosophila melanogaster
Ammonia and its amine-containing derivatives are widely found in natural decomposition byproducts. Here, we conducted biased chemoreceptor screening to investigate the mechanisms by which different concentrations of ammonium salt, urea, and putrescine in rotten fruits affect feeding and oviposition behavior. We identified three ionotropic receptors, including the two broadly required IR25a and IR76b receptors, as well as the narrowly tuned IR51b receptor. These three IRs were fundamental in eliciting avoidance against nitrogenous waste products, which is mediated by bitter-sensing gustatory receptor neurons (GRNs). The aversion of nitrogenous wastes was evaluated by the cellular requirement by expressing Kir2.1 and behavioral recoveries of the mutants in bitter-sensing GRNs. Furthermore, by conducting electrophysiology assays, we confirmed that ammonia compounds are aversive in taste as they directly activated bitter-sensing GRNs. Therefore, our findings provide insights into the ecological roles of IRs as a means to detect and avoid toxic nitrogenous waste products in nature.Dhakal et al. use chemoreceptor screening on three ionotropic receptors in Drosophila, IR25a, IR76b, IR51b to evaluate their impact on avoidance behaviors against nitrogenous waste products. The results of electrophysiology assays show that ammonia compounds are aversive in taste by directly activating bitter-sensing gustatory receptor neurons.
Lake Water Depletion Linkages with Seismic Hazards in Sikkim, India: A Case Study on Chochen Lake
After the 2011 earthquake, lake water depletion has become a widespread issue in Sikkim, especially in regions classified as high to very high seismic zones, where many lakes have turned into seasonal water bodies. This study investigates Chochen Lake in the Barapathing area of Sikkim’s Pakyong district, which is facing severe water seepage and instability. The problem, intensified by the 2011 seismic event and ongoing local construction, is examined through subsurface fracture mapping using Vertical Electrical Sounding (VES) and profiling techniques. A statistical factor method, applied to interpret VES data, helped identify fracture patterns beneath the lake. Results from two sites (VES-1 and VES-2) reveal significant variations in weathered and semi-weathered soil layers, indicating fractures at depths of 17–50 m (VES-1) and 20–55 m (VES-2). Higher fracture density near VES-1 suggests increased settlement risk and ground displacement compared to VES-2. Contrasting resistivity values emphasize the greater instability in this zone and the need for cautious construction practices. The findings highlight the role of seismic-induced fractures in ongoing water depletion and underscore the importance of continuous dewatering to stabilize the swampy terrain.
Determining Dhap Pokhari lake surface dynamics for restoration strategies through geoelectrical mapping
Lakes in the hilly regions of the Sikkim Himalayas in India are crucial for water supply and tourism. However, this area experiences frequent earthquakes and microtremors, increasing the risk of seismic hazards and contributing to a higher density of subsurface fractures and discontinuities. This has led to water seepage in lakes across Sikkim, turning some from perennial to seasonal. To investigate these issues, geoelectrical mapping techniques, specifically Vertical Electrical Sounding (VES) and profiling, were used to study Dhap Pokhari Lake in Sikkim’s Pakyong district. The findings revealed a subsurface fracture zone beginning at a depth of 20 m and extending down to 50 m. The VES data showed significant variations in sediment thickness and subsurface lithology between two measurement points only 10 m apart, with a noticeable ground settlement of about 2 m at one location. The profiling results indicated a major fracture and two minor ones, which are likely causing water seepage and ground saturation, particularly during rainy seasons, leading to compaction and ground settlement. This poses a risk to the structural stability of the surrounding areas, highlighting the need for effective lake restoration strategies. Geoelectrical mapping is a valuable tool for identifying such subsurface fractures and making evidence-based strategies to revive lakes in this seismically active region.
Thermodynamic Properties of Liquid Toluene from Speed-of-Sound Measurements at Temperatures from 283.15 K to 473.15 K and at Pressures up to 390 MPa
We report the speeds of sound in liquid toluene (methylbenzene) measured using double-path pulse-echo apparatus independently at The University of Western Australia (UWA) and Imperial College London (ICL). The UWA data were measured at temperatures between (306 and 423) K and at pressures up to 65 MPa with standard uncertainties of between (0.02 and 0.04)%. At ICL, measurements were made at temperatures between (283.15 and 473.15) K and at pressures up to 390 MPa with standard uncertainty of 0.06%. By means of thermodynamic integration, the measured sound-speed data were combined with initial density and isobaric heat capacity values obtained from extrapolated experimental data to derive a comprehensive set of thermodynamic properties of liquid toluene over the full measurement range. Extensive uncertainty analysis was performed by studying the response of derived properties to constant and dynamic perturbations of the sound-speed surface, as well as the initial density and heat capacity values. The relative expanded uncertainties at 95% confidence of derived density, isobaric heat capacity, isobaric expansivity, isochoric heat capacity, isothermal compressibility, isentropic compressibility, thermal pressure coefficient and internal pressure were estimated to be (0.2, 2.2, 1.0, 2.6, 0.6, 0.2, 1.0 and 2.7)%, respectively. Due to their low uncertainty, these data and derived properties should be well suited for developing a new and improved fundamental Helmholtz equation of state for toluene.
Building sustainability in the Eastern Himalaya: linking evidence to action
Operating at the science, policy, practice interface (SPPI) is often contentious, as knowledge creators and end-users seldom engage, preferring to operate in their own worlds. The application of science to solve sustainability challenges has not received the desired attention, especially in developing countries. How to strengthen the credibility, relevance and legitimacy of research so as to enhance the chances of uptake in decision making? How to generate knowledge differently, so that it is more likely to bring about change and benefit society? The purpose of this research is to examine these questions in the context of three sustainability case studies that were able to transcend the knowledge action barrier. These case studies are from the global biodiversity hot spot of Eastern Himalaya, India, and cover the themes of sustainability of pastoral systems, promoting sustainable livelihoods for the poor and co-designing a Himalayan spring revival initiative. The findings are structured to highlight how the demand for science arose, findings of the research and how the knowledge generated was translated into action. The results show that firstly relevance of science increases manifold when aligned to prominent policy decisions and real-world problems. Secondly, trans-disciplinary studies that synthesize social, economic and ecological aspects have a greater chance of influencing policy makers. Thirdly, mediation by science stewards holds lot of promise in connecting the worlds of academicians and policy makers. The study provides practical guidance on bridging the SPPI and contributes to the growing body of the literature on sustainability science.
TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells
Understanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Previously, we demonstrated the role of TRPγ in nutrient-sensing behavior (Dhakal et al., 2022). Here, we found that a TRPγ mutant exhibited in Drosophila melanogaster is required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) of D. melanogaster . Interestingly, trpγ deficient mutants exhibited elevated TAG levels and our genetic data indicated that Dh44 neurons are indispensable for normal lipid storage but not protein storage. The trpγ mutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated that trpγ knockout downregulated brummer , a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulate nutrient storage.
A single pair of pharyngeal neurons functions as a commander to reject high salt in Drosophila melanogaster
Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster , internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b , is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.