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Search Results: 1 - 10 of 493749 matches for " M. K. Raghuraman "
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Functional Centromeres Determine the Activation Time of Pericentric Origins of DNA Replication in Saccharomyces cerevisiae
Thomas J. Pohl,Bonita J. Brewer,M. K. Raghuraman
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002677
Abstract: The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in early replicating domains, a property conserved among centromeres in fungi and some higher eukaryotes. Surprisingly, little is known about the biological significance or the mechanism of early centromere replication; however, the extensive conservation suggests that it is important for chromosome maintenance. Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time. Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain. We used a modified Meselson-Stahl density transfer assay to measure the kinetics of replication for regions of chromosome XIV in which either the functional centromere or a point-mutated version had been moved near origins that reside in a late replication region. We show that a functional centromere acts in cis over a distance as great as 19 kb to advance the initiation time of origins. Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation.
Origin-Dependent Inverted-Repeat Amplification: A Replication-Based Model for Generating Palindromic Amplicons
Bonita J. Brewer ,Celia Payen,M. K. Raghuraman,Maitreya J. Dunham
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002016
Abstract:
Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification
Bonita J. Brewer?,Celia Payen?,Sara C. Di Rienzi?,Megan M. Higgins?,Giang Ong?,Maitreya J. Dunham?,M. K. Raghuraman
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005699
Abstract: DNA replication errors are a major driver of evolution—from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model—Origin-Dependent Inverted-Repeat Amplification (ODIRA)—proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error—the ligation of leading and lagging nascent strands to create “closed” forks—can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent—a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial, inverted CNVs pivotal in human health and evolution.
A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan
Elizabeth X. Kwan,Eric J. Foss,Scott Tsuchiyama,Gina M. Alvino,Leonid Kruglyak,Matt Kaeberlein,M. K. Raghuraman,Bonita J. Brewer,Brian K. Kennedy,Antonio Bedalov
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003329
Abstract: Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics.
GC-Rich DNA Elements Enable Replication Origin Activity in the Methylotrophic Yeast Pichia pastoris
Ivan Liachko,Rachel A. Youngblood,Kyle Tsui,Kerry L. Bubb,Christine Queitsch,M. K. Raghuraman,Corey Nislow,Bonita J. Brewer,Maitreya J. Dunham
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004169
Abstract: The well-studied DNA replication origins of the model budding and fission yeasts are A/T-rich elements. However, unlike their yeast counterparts, both plant and metazoan origins are G/C-rich and are associated with transcription start sites. Here we show that an industrially important methylotrophic budding yeast, Pichia pastoris, simultaneously employs at least two types of replication origins—a G/C-rich type associated with transcription start sites and an A/T-rich type more reminiscent of typical budding and fission yeast origins. We used a suite of massively parallel sequencing tools to map and dissect P. pastoris origins comprehensively, to measure their replication dynamics, and to assay the global positioning of nucleosomes across the genome. Our results suggest that some functional overlap exists between promoter sequences and G/C-rich replication origins in P. pastoris and imply an evolutionary bifurcation of the modes of replication initiation.
Optimization Of Edm Parameters Using Taguchi Method And Grey Relational Analysis For Mild Steel Is 2026
RAGHURAMAN S, THIRUPPATHI K, PANNEERSELVAM T, SANTOSH S
International Journal of Innovative Research in Science, Engineering and Technology , 2013,
Abstract: Optimization is one of the techniques used in manufacturing sectors to arrive for the best manufacturing conditions, which is an essential need for industries towards manufacturing of quality products at lower cost. This paper aims to investigate the optimal set of process parameters such as current, pulse ON and OFF time in Electrical Discharge Machining (EDM) process to identify the variations in three performance characteristics such as rate of material removal, wear rate on tool, and surface roughness value on the work material for machining Mild Steel IS 2026 using copper electrode. Based on the experiments conducted on L9 orthogonal array, analysis has been carried out using Grey Relational Analysis, a Taguchi method. Response tables and graphs were used to find the optimal levels of parameters in EDM process. The confirmation experiments were carried out to validate the optimal results. Thus, the machining parameters for EDM were optimized for achieving the combined objectives of higher rate of material removal, lower wear rate on tool, and lower surface roughness value on the work material considered in this work. The obtained results show that the Taguchi Grey relational Analysis is being effective technique to optimize the machining parameters for EDM process.
Quality Improvement through First Pass Yield using Statistical Process Control Approach
R. Raj Mohan,K. Thiruppathi,R. Venkatraman,S. Raghuraman
Journal of Applied Sciences , 2012,
Abstract: The objective of this study was to improve First Pass Yield (FPY) and reduce the defect rate of a product. Nowadays, the competitive manufacturing background illustrates that the customers always demanding higher quality in product. Therefore, suppliers strive to satisfy the customer needs beside they are trying to reduce the operating cost and to stay profitable. To survive in a spirited market, improving quality of product is must for any company. In this study, data regarding quantity output of good parts and defective parts has been collected from daily check sheet, critical issues related to defective parts were identified using Pareto analysis chart and its root causes were identified using fishbone diagram. Finally, improvement action plan for critical issues were suggested for quality improvement. After the accomplishment of the action plan, the existing first pass yield is compared with the preliminary first pass yield and substantial improvement in first pass yield attained indicates that defect rate decline with improvement in quality.
Experimental Investigations on Delamination to Improve the Hole Quality in Chopped Strand Mat GFRP Material During Drilling Operation
T. Panneerselvam,S. Raghuraman
Journal of Applied Sciences , 2012,
Abstract: Fiber Reinforced Composite materials have an increased applications in recent days due to its enhanced structural properties and in turn mechanical and thermal properties. The heterogeneous nature of this kind of material makes complications in machining operation. However, drilling is a common machining practice for assembly of components. The quality of holes produced in Chopped Strand Mat Glass Fiber Reinforced Plastic (CSMat GFRP) material is severely affected by internal delamination besides with entry and exit delamination. The objective of the study was to apply the Taguchi methods to achieve an improved hole quality considering minimum delamination through proper selection of drilling parameters. A plan of experiments based on orthogonal main effect design has been used to get data for analysis. The signal to noise ratio and the analysis of variance are employed to investigate the drilling characteristics of CSMat GFRP material using high speed steel drills.
Glacial Cycles and Milankovitch Forcing
Shiv Priyam Raghuraman
Physics , 2015,
Abstract: Using a recent conceptual model of the glacial-interglacial cycles we present more evidence of Milankovitch cycles being the trigger for retreat and forming of ice sheets in the cycles. This model is based on a finite approximation of an infinite dimensional model which has three components: Budyko's energy balance model describing the annual mean temperatures at latitudes, Widiasih's ODE which describes the behavior of the edge of the ice sheet, and Walsh et al. who introduced a snow line to account for glacial accumulation and ablation zones. Certain variables in the model are made to depend on the Milankovitch cycles, in particular, the obliquity of the Earth's axis and the eccentricity of the Earth's orbit. We see as a result that deglaciation and glaciation do occur mostly due to obliquity and to some extent eccentricity.
Reserpine Improves Working Memory  [PDF]
Raghuraman Vasantharaja, Ajeet Kumar, Ashok Kumar, Jamuna R. Subramaniam
Journal of Behavioral and Brain Science (JBBS) , 2016, DOI: 10.4236/jbbs.2016.63012
Abstract: Despite exhaustive search, no drug is in sight for AD. Earlier, we reported that reserpine, an antihypertensive and antipsychotic drug, ameliorates Amyloid beta (Aβ-AD causing peptide) toxicity and confers several positive enhancements in the C. elegans model system. Here, we evaluate whether reserpine can provide protection against working memory and against AD in the mouse model. Reserpine (0.08 mg) was administered orally on alternate days to the non-Tg and accelerated Aβ deposition (at 2 months of age)and cognitive deficit (4 months of age) developing 5XFAD AD Tg mouse model expressing mutant human APP (3 familial mutations) and human Presenilin1(2 familial mutations) in the neurons, and follow their working memory for 2 months using the spontaneous Y-maze alteration behavioral paradigm. Reserpine enhanced working memory in non-Tg mice and improved the cognitive deficit in the 5XFAD AD Tg mice. Hence, reserpine can be considered for a detailed evaluation in the 3X Tg AD mouse model and a pilot study in AD patients.
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