http://localhost:8081/jspui/handle/123456789/109 Sat, 17 Oct 2026 15:27:54 GMT 2026-10-17T15:27:54Z http://localhost:8081/jspui/handle/123456789/21505 Title: Analysis of ApoE4’s role in influencing the cognitive status of patients via microglia signaling in Alzheimer’s disease Authors: Deo, Aayushi Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease affecting individuals of age 60+ years. A combination of genetic and environmental factors are responsible for the disease. The major pathophysiology associated with the disease is accumulation of Amyloid beta plaques and neurofibrillary tangles (tauopathy). Several genes through Genome wide sequencing studies (GWAS) have been found to be a risk factor in the disease progression. One such gene is ApoE whose allelic variant ApoE4 has a high risk of disease development. Glial cells play a central role in the disease pathophysiology. The focus of this study is to analyze the relationship between the Apoe4 allele and tauopathy in glial cells in AD patients at different Braak staging and cognition levels. For this, the study was divided into three parts. The first analysis was based on the Aging, Dementia and Traumatic Brain Injury (TBI) Project from the Adult Changes in Thought (ACT) study. The study spanned across three anatomical brain sections- Temporal cortex, Hippocampus and Parietal cortex. For the second part of analysis, the data was accessed from the same ACT study at the University of Washington Alzheimer’s Disease Research Center (ADRC) without any history of TBI. This data was further segregated into dementia and non dementia patient cohorts. In both the studies, microglial markers IBA1, tauopathy markers AT8 and NeuN markers were studied to produce a numerical expression value for statistical analysis. In the first part of the study, it was observed that the presence of ApoE4 did not directly influence tauopathy in a cohort of traumatic brain injury (TBI) patients. However, tauopathy increased when progressing from Braak stage 0-2 to Braak stage 5-6, but there was no significant effect on microglia levels, as indicated by constant IBA1 levels in three brain tissues (hippocampus, parietal cortex, and temporal cortex) that are commonly affected in Alzheimer's disease (AD).In the second part of the study, ApoE4 was found to influence microgliosis in dementia patients with the allele, and its absence also had an impact on the pathophysiology of cognitively resilient non-dementia patients. In ApoE4-positive dementia patients, ApoE4 was associated with increased tauopathy compared to non-dementia patients with the allele. In the absence of ApoE4, cognitively resilient patients showed increased microgliosis, which was found to be protective rather than toxic, unlike in the presence of ApoE4. This increased microgliosis could potentially explain the cognitive resilience observed in ApoE4-negative patients, as it may lead to an increased population of neuroprotective microglial cells. However, ApoE4 had no significant effect on astrocytic cells, as indicated by no significant change in GFAP process area in cognitively resilient non-dementia patients. Sat, 01 Apr 2023 00:00:00 GMT http://localhost:8081/jspui/handle/123456789/21505 2023-04-01T00:00:00Z http://localhost:8081/jspui/handle/123456789/21504 Title: Investigating the functional conservance and divergence of OsHD genes across plant species Authors: Kushwaha, Akash Singh Abstract: Roots are key to plants for nutrition and water uptake. Studying root architecture to understand its response to stress condition and genetic factors underlying it, is important to create high yield crops. Since the evolution and proliferation of life forms from aquatics to terrestrial habitat, plants required a well-developed efficient system to absorb nutrients from the surroundings. Functional divergence in parallel with gene amplification and duplication are the vital players of evolution. One such example is Arabidopsis stem cell regulator WUSCHEL (WUS), besides WUSCHEL-related homeobox (WOX named after WUS). They possess conserved homeodomain for their function. These are master regulators of key developmental programs i.e., stem cell maintenance, cellular reprogramming, cell fate determination, fertility, stem, root and leaf development, apical meristem maintenance amongst others. Some of these transcription factors are evolutionary conserved for their functions in root development perspective across monocots and dicots others have divergent function. Rice HD factors are very well known to control shoot borne adventitious root development (establishment, initiation, and emergence). This study will focus on investigating the role of OsHD genes in Arabidopsis in temporal control manner to analyze the surfeit of functional conservancy and divergence in its functioning vis-à-vis root architecture. Sat, 01 Apr 2023 00:00:00 GMT http://localhost:8081/jspui/handle/123456789/21504 2023-04-01T00:00:00Z http://localhost:8081/jspui/handle/123456789/21503 Title: Identification and evaluation of small molecules targeting NS5 methyltransferase activity of Dengue Virus Authors: Pathak, Akashjyoti Abstract: Dengue virus (DENV) is a major global health threat, causing endemic diseases with approximately 2 lakh cases annually in India alone. DENV replication is complex and relies on the host cellular machinery, making it a challenging target for antiviral intervention. The NS5 protein, a nonstructural protein of DENV, has methyltransferase (MTase) activity that catalyzes methylation of the viral RNA cap using S-Adenosyl-L-methionine (SAM) as a substrate. This step is crucial for viral translation and replication. The conservation of the SAM binding pocket in the MTase domain of NS5 across flaviviruses makes it a promising target for the development of small molecule inhibitors with broad spectrum antiviral activity. In this study, the NS5 MTase protein was expressed, purified, and crystallized to facilitate structural studies. Two compounds with reported inhibitory activity against the MTase of other viruses were selected for evaluation, and their binding affinity was determined using fluorescence spectroscopy. Site-directed mutagenesis was also performed to generate negative control mutants for comparative analysis. Co-crystallization and soaking techniques were employed to elucidate the protein-ligand complex structure. The findings of this project have significant implications for the development of effective antiviral therapies against DENV. The identification of small molecule inhibitors against the NS5 MTase domain of DENV can disrupt viral replication and translation, and potentially lead to the development of novel antiviral strategies. Moreover, the insights gained from this research can also aid in the development of inhibitors against other flaviviruses that share similar MTase structures and functions. Overall, this study contributes to the field of antiviral drug discovery and addresses the unmet medical need for the management of flavivirus infections, including DENV, providing a valuable foundation for future research in this area. Mon, 01 May 2023 00:00:00 GMT http://localhost:8081/jspui/handle/123456789/21503 2023-05-01T00:00:00Z http://localhost:8081/jspui/handle/123456789/21502 Title: SFSC (Spectral SSNR-based Fourier Shell Correlation) based alignment and clustering of cryo-electron subtomograms Authors: Mandal, Angshuman Abstract: The quality of a 3-D structure obtained by averaging a subtomogram cluster in Cryo-Electron Tomography majorly depends upon the alignment of the subtomograms within the cluster and contamination concerning the membership of particles with similar structural organization. SFSC is a robust and fast quality score that can efficiently rank subtomogram clusters of large sizes. In a comparative analysis of more than 15 scoring functions, it was found that SFSC was better and more efficient in ranking subtomogram clusters when compared to other scoring functions frequently used as a standard to assess the quality of a cluster. Currently, constrained cross correlation is used as a standard alignment metric to align subtomograms in a cluster. However, it has limitations like statistical fluctuations in considering missing wedges due to the random splitting of the set of subtomograms into two and the ability to work on limited sample size due to its pairwise alignment nature. These limitations can be tackled by using SFSC as a metric to align the subtomograms in a cluster to produce high-quality scores indicating better quality of the subtomogram averages. In this study, we intend to develop an alignment algorithm based on the SFSC function, implement it on simulated and experimental cellular subtomogram clusters, and compare it to the existing constrained cross-correlation method (missing wedge as a constraint), a standard method used for subtomogram alignment, in terms of the resolution of subtomogram averages produced by the two methods. Thu, 01 Jun 2023 00:00:00 GMT http://localhost:8081/jspui/handle/123456789/21502 2023-06-01T00:00:00Z