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Lakshminath Bezbaroa Central Library Digital Repository
Welcome to the Institutional Digital Repository of Lakshminath Bezbaroa Central Library.
- This digital archive comprised of the Institutes' intellectual output.
- It manages, preserves & makes available the academic works of faculty and research scholars.
- It is established to facilitate deposit of digital content of scholarly or heritage nature.
- Allowing academics & their departments to share & preserve contents in a managed environment.
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To gain insights into the function of yeast Dnm1 in mitochondrial dynamics
Mitochondria, vital hubs of cellular metabolism, continuously modulate their shape and number through fission and fusion. The central mediator of mitochondrial fission is the GTPase Dnm1 in yeast, and its homolog DRP1 in humans. Dnm1 comprises four domains - an N-terminal GTP-binding domain, a middle domain, a variable B-insert domain, and a C-terminal GTPase effector domain. Dnm1 undergoes assembly/disassembly cycles driven by GTP binding and hydrolysis to facilitate fission. While substantial progress has been made in understanding the domain architecture, function, and interacting partners of Dnm1, critical aspects, including the regulation of oligomeric forms, their spatio-temporal distribution, and the impact of post-translational modifications (PTMs), remain unclear. Moreover, disruptions in the delicate balance between mitochondrial function and dynamics are associated with various human diseases, with specific mutations in DRP1 linked to pathological conditions. Despite previous studies on the effects of these mutations on mitochondrial morphology, their impact on protein localization, distribution, function, and structure remains unexplored. This study aimed to investigate specific residues in Dnm1 that may undergo modifications or are mutated in disease conditions, examining their impact on the protein's structure, localization, and function. To achieve this, functional FL-Dnm1-GFP and Dnm1-HisHA fusion proteins were constructed, for in vivo and in vitro assessment, respectively. Five putative Dnm1 phosphorylation sites were selected for mutagenesis based on stringent conservation criteria. Interestingly, mutating S624, analogous to the reported regulatory DRP1 S616 site, did not affect mitochondrial morphology in yeast. However, mutating T62 and S277 in G2 and G5 motifs of the GTPase domain yielded non-functional proteins despite differences in their localization and dynamics. Structurally, T62A/D formed atypical large puncta, while S277A/D resembled WT Dnm1. Further computational analyses and molecular dynamics simulations provided insights into conformational changes and altered atomistic motion, particularly highlighting the dominant-negative impact of S277 mutation without altering protein localization. Furthermore, the study extended the investigation to mimic four disease-causing DRP1 mutations in Dnm1, uncovering diverse functional outcomes. For instance, the A430D mutation led to a complete loss of Dnm1 function, disrupting typical punctate phenotypes and presence of diffused cytosolic fluorescence, indicating defective oligomerization. Simulations revealed the mutation induced major conformational and dynamics changes in a helix region. In contrast, the G397D mutation resulted in fewer, larger, and less dynamic puncta, likely due to change in orientation of a loop surrounding the mutated residue. Thus, investigating each mutation in detail is crucial for gaining insights into their respective roles in disease-associated alterations of mitochondrial dynamics. In conclusion, this research provides novel insights into the molecular basis of Dnm1 function and regulation, contributing to a deeper understanding of conserved mitochondrial fission processes. Additionally, it paves the way for the development of targeted therapies for several neurological diseases where mitochondrial fission-fusion regulation is impaired.
Cell functions and molecular mechanisms of zinc transporters in Neurospora crassa
"Thesis Title: Cell functions and molecular mechanisms of zinc transporters in Neurospora crassa In this thesis work, I studied the cellular functions and molecular mechanisms of zinc resistance-conferring 1 (ZRC-1), meiotic sister chromatid 2 (MSC-2), and zinc-regulated gene 17 (ZRG-17) that are members of the cation diffusion facilitator (CDF) family of zinc transporters in Neurospora crassa. The Δzrc-1 mutant was unable to grow under high zinc conditions (≥ 0.5 mM). However, the expression of zrc-1 was elevated ~3-fold under low zinc conditions in comparison to normal and high zinc concentrations. The Δmsc-2 mutant showed colony growth and aerial hyphae similar to wild type and the expression of msc-2 was independent of zinc. Furthermore, the double mutant Δzrc-1; Δmsc-2 and Δzrc-1; Δzrg-17 showed additive phenotypes of both the parental single mutants. However, the phenotypic defects such as slow growth rate, defective in asexual sporulation, and inability to degrade cellulose of the Δzrg-17 single mutant were restored in the Δmsc-2; Δzrg-17 double mutant, which showed phenotypes similar to the wild type. The double mutant Δzrc-1; Δzrg-17 showed severe growth defects, stunted aerial hyphae, short septa, and defects in conidiation. In addition, the Δzrc-1; Δmsc-2 and Δzrc-1; Δzrg-17 double mutants showed sensitivity to DTT-induced ER stress and were unable to grow in the medium containing cellulose. Furthermore, zinc-responsive activator protein 1 (ZAP-1) was also studied to understand the molecular mechanism and the interaction of the CDF zinc transporters with the transcription factor. The zap-1 of N. crassa was found to be crucial for survival under low zinc conditions and ZAP-1 was localized in nucleus under all zinc conditions tested. The double mutants Δzap-1; Δzrc-1, Δzap-1; Δmsc-2, and Δzap-1; Δzrg-17 showed slow growth under low zinc like Δzap-1, indicating that ZAP-1 might be functioning upstream of zrc-1, msc-2, and zrg-17. Furthermore, expression analysis of the CDF family of zinc transporter, zrc-1, msc-2, zrg-17, and zrt-3 in Δzap-1 mutant showed very low-level expressions compared to expression in wild type, indicating that the ZAP-1 transcription factor regulates the CDF zinc transporters under low zinc conditions."
Design and Implementation of Hardware-Efficient Architectures for FFT Algorithms
The Fast Fourier Transform (FFT) holds significance across diverse applications in wireless communications, audio, and signal processing. This doctoral thesis addresses the imperative need to enhance hardware efficiency while concurrently minimizing area and power consumption in FFT processors. Extensive efforts by researchers have centered on optimizing FFT algorithms, determining the requisite number of multipliers, adders, and registers, all of which intricately influence power consumption and overall area. These considerations become pivotal constraints in FFT applications, necessitating a judicious trade-off between complexity and performance.
Effective Utilization of Data for Enhancing the Performance of Manufacturing
The effective utilization of data is becoming increasingly important for enhancing the performance of manufacturing processes. In the era of Industry 4.0, advancements in technology have enabled the collection of vast amounts of data from various manufacturing processes, making it possible to analyze the data and derive insights that can help enhance the performance. One of the main advantages of using data-driven manufacturing is the ability to identify quality issues early in the production process. It reduces the likelihood of defective products, thereby enhancing customer satisfaction, reducing wastage and improving the profitability.
Experimental and Computational Studies on Exit-Hole-Free Friction Stir Spot Welding Processes
This thesis contributes to understanding friction stir spot welding (FSSW) by investigating friction, heat generation and exit-hole elimination. Lubricants were applied during FSSW of aluminum alloy sheets resulting in a 44–55% reduction in torque and 12–24% reduction in plunge force requirements. More than 50% reduction in energy requirement while maintaining good joint strength is observed. This suggested the more important role of plastic deformation in heat generation as compared to friction. The study introduces an inverse approach to model friction during FSSW, utilizing finite element (FE) simulations in DEFORM 3D and validating with experiments. Further, this thesis investigates ways of producing exit-hole-free welds during FSSW. In one method the exit-hole is filled with waste aluminum chips and friction stir processing is performed over it. The process delivered 16% and 84% higher load-bearing capacities during T-peel tests compared to conventional FSSW with and without pin, respectively. A novel method of using consumable pin during FSSW is introduced to produce exit-hole-free joints. The feasibility and performance of FSSW using three consumable pin materials viz., AA6061-T6, mild steel and oil hardened non-shrinking die steel, are explored. Additionally, the research evaluates the impact of rotational speed and plunge rate on joint quality. It is found that the joint strength increases with increase in rotational speed up to 900 RPM and further increase in rotational speed decreases joint strength. A 1.7 times increase in joint strength at 900 RPM compared to 360 RPM is achieved. On the other hand, optimum plunge rate for highest joint strength is found to be 15 mm/min. A 4% increase in lap shear strength at 15 mm/min plunge rate compared to 6 mm/min, with an 8.5% decrease in energy requirements is obtained. A good match between experiments and FE simulations is obtained. Adhesive-bonded consumable pin along with application of lubrication is suggested for industrial application, which results in faster production speed and lower energy requirement while delivering good joint quality. This study provides a comprehensive understanding of FSSW, spanning friction, heat generation, exit-hole-free FSSW joints, parametric study and the integration of lubricants and adhesive-bonded consumable pins.