29 results on '"Maganti, S."'
Search Results
2. Involvement of Target of Rapamycin (TOR) Signaling in the Regulation of Crosstalk between Ribosomal Protein Small Subunit 6 Kinase-1 (RPS6K-1) and Ribosomal Proteins
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Achala Bakshi, Mazahar Moin, Meher B. Gayatri, Aramati B. M. Reddy, Raju Datla, Maganti S. Madhav, and Pulugurtha B. Kirti
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target of rapamycin ,ribosomal proteins large subunit genes ,ribosomal proteins small subunit genes ,Botany ,QK1-989 - Abstract
The target of rapamycin (TOR) protein phosphorylates its downstream effector p70kDa ribosomal protein S6 kinases (S6K1) for ribosome biogenesis and translation initiation in eukaryotes. However, the molecular mechanism of TOR-S6K1-ribosomal protein (RP) signaling is not well understood in plants. In the present study, we report the transcriptional upregulation of ribosomal protein large and small subunit (RPL and RPS) genes in the previously established TOR overexpressing transgenic lines of rice (in Oryza sativa ssp. indica, variety BPT-5204, TR-2.24 and TR-15.1) and of Arabidopsis thaliana (in Col 0 ecotype, ATR-1.4.27 and ATR-3.7.32). The mRNA levels of RP genes from this study were compared with those previously available in transcriptomic datasets on the expression of RPs in relation to TOR inhibitor and in the TOR-RNAi lines of Arabidopsis thaliana. We further analyzed TOR activity, i.e., S6K1 phosphorylation in SALK lines of Arabidopsis with mutation in rpl6, rpl18, rpl23, rpl24 and rps28C, where the rpl18 mutant showed inactivation of S6K1 phosphorylation. We also predicted similar putative Ser/Thr phosphorylation sites for ribosomal S6 kinases (RSKs) in the RPs of Oryza sativa ssp. indica and Arabidopsis thaliana. The findings of this study indicate that the TOR pathway is possibly interlinked in a cyclic manner via the phosphorylation of S6K1 as a modulatory step for the regulation of RP function to switch ‘on’/‘off’ the translational regulation for balanced plant growth.
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- 2023
- Full Text
- View/download PDF
3. RNA-seq of Rice Yellow Stem Borer Scirpophaga incertulas Reveals Molecular Insights During Four Larval Developmental Stages
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Pichili Renuka, Maganti S. Madhav, Ayyagari Phani Padmakumari, Kalyani M. Barbadikar, Satendra K. Mangrauthia, Kola Vijaya Sudhakara Rao, Soma S. Marla, and Vemuri Ravindra Babu
- Subjects
insect ,Scirpophaga incertulas ,de novo transcriptome ,RNAi ,growth and development ,detoxification mechanism ,Genetics ,QH426-470 - Abstract
The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ∼229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches.
- Published
- 2017
- Full Text
- View/download PDF
4. Involvement of Target of Rapamycin (TOR) Signaling in the Regulation of Crosstalk between Ribosomal Protein Small Subunit 6 Kinase-1 (RPS6K-1) and Ribosomal Proteins
- Author
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Bakshi, Achala, primary, Moin, Mazahar, additional, Gayatri, Meher B., additional, Reddy, Aramati B. M., additional, Datla, Raju, additional, Madhav, Maganti S., additional, and Kirti, Pulugurtha B., additional
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- 2023
- Full Text
- View/download PDF
5. Diverse Rice Landraces of North-East India Enables the Identification of Novel Genetic Resources for Magnaporthe Resistance
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Bangale Umakanth, Balija Vishalakshi, P. Sathish Kumar, S. J. S. Rama Devi, Vijay Pal Bhadana, P. Senguttuvel, Sudhir Kumar, Susheel Kumar Sharma, Pawan Kumar Sharma, M. S. Prasad, and Maganti S. Madhav
- Subjects
rice landrace ,blast resistance ,genetic diversity ,population structure ,core set ,association mapping ,Plant culture ,SB1-1110 - Abstract
North-East (NE) India, the probable origin of rice has diverse genetic resources. Many rice landraces of NE India were not yet characterized for blast resistance. A set of 232 landraces of NE India, were screened for field resistance at two different hotspots of rice blast, viz., IIRR-UBN, Hyderabad and ICAR-NEH, Manipur in two consecutive seasons. The phenotypic evaluation as well as gene profiling for 12 major blast resistance genes (Pitp, Pi33, Pi54, Pib, Pi20, Pi38, Pita2, Pi1, Piz, Pi9, Pizt, and Pi40) with linked as well as gene-specific markers, identified 84 resistant landraces possessing different gene(s) either in singly or in combinations and also identified seven resistant landraces which do not have the tested genes, indicating the valuable genetic resources for blast resistance. To understand the molecular diversity existing in the population, distance and model based analysis were performed using 120 SSR markers. Results of both analyses are highly correlated by forming two distinct subgroups and the existence of high diversity (24.9% among the subgroups; 75.1% among individuals of each subgroup) was observed. To practically utilize the diversity in the breeding program, a robust core set having an efficiency index of 0.82 which consists of 33 landraces were identified through data of molecular, blast phenotyping, and important agro-morphological traits. The association of eight novel SSR markers for important agronomic traits which includes leaf and neck blast resistance was determined using genome-wide association analysis. The current study focuses on identifying novel resources having field resistance to blast as well as markers which can be explored in rice improvement programs. It also entails the development of a core set which can aid in representing the entire diversity for efficiently harnessing its properties to broaden the gene pool of rice.
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- 2017
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6. First Beam Commissioning Report of a Novel Medical Linear Accelerator Designed for Biologically Guided Radiotherapy
- Author
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Han, B., primary, Kovalchuk, N., additional, Capaldi, D.P., additional, Simiele, E., additional, White, J., additional, Purwar, A., additional, Yeung, T., additional, Maganti, S., additional, Mitra, A., additional, Voronenko, Y., additional, Oderinde, O.M., additional, Shirvani, S.M., additional, Kuduvalli, G., additional, Vitzthum, L., additional, Chang, D.T., additional, Xing, L., additional, and Surucu, M., additional
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- 2021
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7. Nested Association Mapping (NAM) Populations: Present Status and Future Prospects in the Genomics Era
- Author
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Gireesh, Channappa, primary, Sundaram, Raman. M., additional, Anantha, Siddaiah M., additional, Pandey, Manish K., additional, Madhav, Maganti S., additional, Rathod, Santosha, additional, Yathish, Kondajji R., additional, Senguttuvel, Ponnuvel, additional, Kalyani, Barbadikar M., additional, Ranjith, Ellur, additional, Venkata Subbarao, Lella, additional, Kumar Mondal, Tapan, additional, Swamy, Mallikarjuna, additional, and Rakshit, Sujay, additional
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- 2021
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8. RNA-seq of Rice Yellow Stem BorerScirpophaga incertulasReveals Molecular Insights During Four Larval Developmental Stages
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Renuka, Pichili, primary, Madhav, Maganti S, additional, Padmakumari, Ayyagari Phani, additional, Barbadikar, Kalyani M, additional, Mangrauthia, Satendra K, additional, Vijaya Sudhakara Rao, Kola, additional, Marla, Soma S, additional, and Ravindra Babu, Vemuri, additional
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- 2017
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9. Diverse Rice Landraces of North-East India Enables the Identification of Novel Genetic Resources for Magnaporthe Resistance
- Author
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Umakanth, Bangale, primary, Vishalakshi, Balija, additional, Sathish Kumar, P., additional, Rama Devi, S. J. S., additional, Bhadana, Vijay Pal, additional, Senguttuvel, P., additional, Kumar, Sudhir, additional, Sharma, Susheel Kumar, additional, Sharma, Pawan Kumar, additional, Prasad, M. S., additional, and Madhav, Maganti S., additional
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- 2017
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10. Silencing of CYP6 and APN Genes Affects the Growth and Development of Rice Yellow Stem Borer, Scirpophaga incertulas
- Author
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Vijaya Sudhakara Rao Kola, Maganti S. Madhav, A. P. Padmakumari, P. Renuka, Satendra K. Mangrauthia, S. M. Balachandran, and V. Ravindra Babu
- Subjects
0106 biological sciences ,0301 basic medicine ,Scirpophaga incertulas ,Physiology ,growth and development ,01 natural sciences ,lcsh:Physiology ,03 medical and health sciences ,RNA interference ,Physiology (medical) ,Botany ,Gene silencing ,Bioassay ,bioassays ,Gene ,Original Research ,lcsh:QP1-981 ,biology ,fungi ,yellow stem borer-YSB ,double stranded RNA (dsRNA) ,cytochrome P450 (CYP6) ,biology.organism_classification ,Cell biology ,010602 entomology ,RNA silencing ,030104 developmental biology ,PEST analysis ,Gene pool ,aminopeptidase N (APN) - Abstract
RNAi is a powerful tool to target the insect genes involved in host-pest interactions. Key insect genes are the choice for silencing to achieve pest derived resistance where resistance genes are not available in gene pool of host plant. In this study, an attempt was made to determine the effect of dsRNA designed from two genes Cytochrome P450 derivative (CYP6) and Aminopeptidase N (APN) of rice yellow stem borer (YSB) on growth and development of insect. The bioassays involved injection of chemically synthesized 5ꞌ FAM labeled 21-nt dsRNA into rice cut stems and allowing the larvae to feed on these stems which resulted in increased mortality and observed growth and development changes in larval length and weight compared with its untreated control at 12-15 days after treatment. These results were further supported by observing the reduction in transcripts expression of these genes in treated larvae. Fluorescence detection in treated larvae also proved that dsRNA was readily taken by larvae when fed on dsRNA treated stems. These results from the present study clearly show that YSB larvae fed on dsRNA designed from Cytochrome P450 and Aminopeptidase N has detrimental effect on larval growth and development. These genes can be deployed to develop YSB resistance in rice using RNAi approach.
- Published
- 2015
11. Silencing of CYP6 and APN Genes Affects the Growth and Development of Rice Yellow Stem Borer, Scirpophaga incertulas
- Author
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Kola, Vijaya Sudhakara Rao, primary, Renuka, P., additional, Padmakumari, Ayyagari Phani, additional, Mangrauthia, Satendra K., additional, Balachandran, Sena M., additional, Ravindra Babu, V., additional, and Madhav, Maganti S., additional
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- 2016
- Full Text
- View/download PDF
12. RNA-seq of Rice Yellow Stem Borer Scirpophaga incertulas Reveals Molecular Insights During Four Larval Developmental Stages.
- Author
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Renuka, Pichili, Madhav, Maganti S., Padmakumari, Ayyagari Phani, Barbadikar, Kalyani M., Mangrauthia, Satendra K., Rao, Kola Vijaya Sudhakara, Marla, Soma S., and Babu, Vemuri Ravindra
- Subjects
- *
SCIRPOPHAGA , *RNA sequencing , *LARVAE - Abstract
The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ~229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
13. Marker-assisted introgression of bacterial blight and blast resistance into IR 58025B, an elite maintainer line of rice
- Author
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Hari, Yadla, primary, Srinivasarao, Kommoju, additional, Viraktamath, Basavaraj C., additional, Hari Prasad, Arremsetty S., additional, Laha, Gouri S., additional, I. Ahmed, Mohammed, additional, Natarajkumar, Podishetty, additional, Sujatha, Kalidindi, additional, Srinivas Prasad, Madamshetty, additional, Pandey, Manish, additional, Ramesha, Mugalodi S., additional, Neeraja, Chirravuri N., additional, Balachandran, Sena M., additional, S. Rani, Nallathigal, additional, Kemparaju, Balachandra, additional, Madhan Mohan, Kolluru, additional, Sama, Venkata S. A. K., additional, Shaik, Hajira, additional, Balachiranjeevi, Chintavaram, additional, Pranathi, Karnati, additional, Ashok Reddy, Gajjala, additional, Madhav, Maganti S., additional, and Sundaram, Raman M., additional
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- 2013
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14. Direct Die Solder of GaAs Power Amplifier Dies and Application of Electrolessly Plated Nickel Barrier
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Shen, H., primary, Maganti, S., additional, and Ramanathan, R., additional
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- 2013
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15. Marker-assisted improvement of a stable restorer line, KMR-3R and its derived hybrid KRH2 for bacterial blight resistance and grain quality
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Hari, Yadla, primary, Srinivasarao, Kommoju, additional, Viraktamath, Basvaraj C., additional, Hariprasad, Arremsetty S., additional, Laha, Gouri S., additional, Ahmed, Mohammed I., additional, Natarajkumar, Podishetty, additional, Ramesha, Mugalodi S., additional, Neeraja, Chirravuri N., additional, Balachandran, Sena M., additional, Rani, Nallathigal S., additional, Balaji Suresh, Pippalla, additional, Sujatha, Kalidindi, additional, Pandey, Manish, additional, Ashok Reddy, Gajjala, additional, Madhav, Maganti S., additional, and Sundaram, Raman M., additional
- Published
- 2011
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16. Molecular Characterization of a Genomic Fragment Containing Pi‐kh Gene from the Genomic Library of Indica Rice Line Tetep
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Madhav, Maganti S., primary, Plaha, Parikshit, additional, Singh, Nagendra K., additional, and Sharma, Tilak R., additional
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- 2009
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17. Genome-wide Identification and Characterization of Transcription Factor Binding Motifs of NBS-LRR Genes in Rice and Arabidopsis.
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Rramkumar, Gandhimani, Madhav, Maganti S., Biswal, Akshaya K., Devi, S.J.S. Rama, Sakthivel, Kannabiran, Mohan, Madhan K., Umakanth, B., Mangrauthia, Satendra K., Sundaram, Raman M., and Viraktamath, Basavaraj C.
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- *
ARABIDOPSIS thaliana genetics , *NUCLEOTIDE sequence , *LEUCINE , *TRANSCRIPTION factors ,RICE genetics - Abstract
Nucleotide binding site leucine rich repeat (NBS-LRR) gene encoding proteins are the major biotic stress resistance genes of rice and Arabidopsis thaliana. Upstream sequences of 206 entire NBS-LRR genes of Arabidopsis and 120 genes of rice were analyzed with three highly reliable motif prediction tools for enhanced accuracy of prediction and characterization of potential transcription factor binding motifs (TFBMs). A total of 36 and 30 novel, strong TFBMs were discovered from NBS-LRR genes of rice and A. thaliana, respectively. All the motifs identifed in these sequences were analyzed for their positional conservation and the possible motif network associations were also identifed. Further, the probability of the presence of motifs in these NBS-LRR genes were validated and statistically tested. Although Arabidopsis NBS-LRR sequences showed 76.3% similarity with rice sequences at motif level, the analysis revealed that rice sequences have many unique TFBMs and are more evolved in gene expression mechanisms. The study also provided a list of novel candidate motifs for these genes, which will be a good resource for experimental validation. A novel strategy of prediction of gene expression based on motif arrangement was also demonstrated in this study. The findings of this study, such as the motifs' positional conservation, architecture, etc. offered new biological insights into the role of TFBMs in the regulation of resistance genes. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Molecular Characterization of a Genomic Fragment Containing Pi-k h Gene from the Genomic Library of Indica Rice Line Tetep.
- Author
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MADHAV, MAGANTI S., PARIKSHIT PLAHA, SINGH, NAGENDRA K., and SHARMA, TILAK R.
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- *
GENE expression , *AMINO acid sequence , *NUCLEOTIDES , *ZINC-finger proteins , *GENOMICS , *MOLECULAR genetics , *LEUCINE , *CLONING , *AMINO acids - Abstract
Identification of full length genes along with upstream regulatory elements is important to understand its expression. Here, we report preparation of high titre genomic library and identification of a genomic clone containing Pi-k h gene with its complete upstream and downstream sequences from the rice blast resistant line Tetep. Structural analysis of protein revealed that Pi-k h has a central nucleotide binding site domain, leucine-rich repeats domain and a unique zinc-finger domain. Comparative analysis of Pi-k h protein sequence showed 64% and 45% similarity with the protein sequences of rice blast resistance genes Pi-b and Pi-ta, respectively. [ABSTRACT FROM AUTHOR]
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- 2009
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19. The role of sialic acid in opsonin-dependent and opsonin-independent adhesion of Listeria monocytogenes to murine peritoneal macrophages.
- Author
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Maganti, S, Pierce, M M, Hoffmaster, A, and Rodgers, F G
- Abstract
The adhesion of listeriae to host cells employs mechanisms which are complex and not well understood. Listeria monocytogenes is a facultative intracellular pathogen responsible for meningoencephalitis, septicemia, and abortion in susceptible and immunocompromised individuals. Subsequent to colonization and penetration of the gut epithelium, the organism attaches to resident macrophages and replicates intracellularly, thus evading the humoral immune system of the infected host. The focus of these studies was to investigate the attachment of the organism to murine peritoneal macrophages in an opsonin-dependent and opsonin-independent fashion. Assessment of competitive binding experiments by immunofluorescence and enzyme-linked immunosorbent assays showed that adhesion of the organism to macrophages in the presence or absence of opsonins was inhibited (90%) by N-acetylneuraminic acid (NAcNeu). In addition, the lectin from Maackia amurensis, with affinity for NAcNeu-alpha(2,3)galactose, blocked binding of L. monocytogenes to host cells. Oxidation of the surface carbohydrates on the organism by using sodium metaperiodate resulted in a dose-dependent reduction (up to 98%) in adherence to macrophages. Monoclonal antibody to complement receptor 3 did not prevent listeriae from binding to mouse macrophages or from replicating within the infected cells whether or not normal mouse serum was present. Based on our results, we propose the involvement of NAcNeu, a member of the sialic acid group, in the attachment of L. monocytogenes to permissive murine macrophages.
- Published
- 1998
20. Insights on Diversity of Leucine-Rich Repeat (LRR) Domain among Major Blast Resistance Genes of Rice.
- Author
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Devi, S.J.S. Rama, Umakanth, B., Vishalakshi, B., Aglawe, Supriya B., Babu, V. Ravindra, and Madhav, Maganti S.
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- *
RICE blast disease , *DARDARIN , *NATURAL immunity - Abstract
Rice blast is a continuous threat in rice ecosystems across the globe; its dynamics is becoming complex in the changing climatic conditions. Host resistance is still a viable option; hence, the exploration of resistance genes and their novel alleles is indispensable. The majority of the blast resistance genes belong to nucleotide-binding site and leucine-rich repeat (LRR) domain. In the present study, diverse LRR alleles of five major blast resistance genes (Pi2, Pi9, Pib, Pita, and Pi37) were cloned from 13 different Oryza species to determine the nucleotide diversity as well as to identify the single nucleotide polymorphisms, InDels, conserved domains, and protein functional sites. Although Pi9 and Pi2 are homologous genes, significant nucleotide variations and variants in the motifs distribution were observed. Among the five genes, Pi37 showed the highest nucleotide diversity and Pita showed the least diversity. The phylogenetic groups of alleles were correlated with the identified haplotypes. The motif (xxLxLxx) was present among all the alleles of blast R gene sequences across various Oryza species, indicating its importance. The appearance of post-translational modification sites in the protein sequences of these alleles also indicates its nature of involvement in host-pathogen interactions. The present study offers clues in further understanding the molecular evolution of the LRR domain of resistance genes, which is a key determinant of host-pathogen interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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21. Racial and ethnic differences in the risk of recurrent preterm or small for gestational age births in the United States: a systematic review and stratified analysis.
- Author
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Dev A, Nagovich J, Maganti S, Vitale E, Blunt H, and Allen SE
- Abstract
Background: The risk of recurrent adverse birth outcomes has been reported worldwide, but there are limited estimates of these risks by social subgroups such as race and ethnicity in the United States. We assessed racial and ethnic disparities in the risk of recurrent adverse birth outcomes, including preterm birth, low birthweight, fetal growth restriction, small for gestational age, stillbirth, and neonatal mortality in the U.S., Methods: We searched MEDLINE, CINAHL Complete, Web of Science, and Scopus from the date of inception to April 5, 2022. We identified 3,540 articles for a title and abstract review, of which 80 were selected for full-text review. Studies were included if they focused on the recurrence of any of the six outcomes listed in the objectives. Study quality was assessed using the NIH Study Quality Assessment Tool. Heterogeneity across studies was too large for meta-analysis, but race and ethnicity-stratified estimates and tests for homogeneity results were reported., Results: Six studies on recurrent preterm birth and small for gestational age were included. Pooled comparisons showed a higher risk of recurrent preterm birth and small for gestational age for all women. Stratified race comparisons showed a higher but heterogeneous risk of recurrence of preterm birth across Black and White women. Relative risks of recurrent preterm birth ranged from 2.02 [1.94, 2.11] to 2.86 [2.40, 3.39] for Black women and from 3.23 [3.07, 3.39] to 3.92 [3.35, 4.59] for White women. The evidence was weak for race and ethnicity stratification for Hispanic and Asian women for both outcomes., Conclusions: Disparities exist in the recurrence of preterm birth, and race/ethnicity-concordant comparisons suggest race is an effect modifier for recurrent preterm birth for Black and White women. Due to the small number of studies, no conclusions could be made for small for gestational age or Hispanic and Asian groups. The results pose new research areas to better understand race-based differences in recurrent adverse birth outcomes., (© 2024. The Author(s).)
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- 2024
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22. Cell polarity proteins promote macropinocytosis in response to metabolic stress.
- Author
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Lambies G, Lee SW, Duong-Polk K, Aza-Blanc P, Maganti S, Dawson DW, and Commisso C
- Abstract
Macropinocytosis has emerged as a nutrient-scavenging pathway that cancer cells exploit to survive the nutrient-deprived conditions of the tumor microenvironment. Cancer cells are especially reliant on glutamine for their survival, and in pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deficiency can enhance the stimulation of macropinocytosis, allowing the cells to escape metabolic stress through the production of extracellular-protein-derived amino acids. Here, we identify the atypical protein kinase C (aPKC) enzymes, PKCζ and PKCι as novel regulators of macropinocytosis. In normal epithelial cells, aPKCs are known to regulate cell polarity in association with the scaffold proteins Par3 and Par6, controlling the function of several targets, including the Par1 kinases. In PDAC cells, we identify that each of these cell polarity proteins are required for glutamine stress-induced macropinocytosis. Mechanistically, we find that the aPKCs are regulated by EGFR signaling or by the transcription factor CREM to promote the relocation of Par3 to microtubules, facilitating macropinocytosis in a dynein-dependent manner. Importantly, we determine that cell fitness impairment caused by aPKC depletion is rescued by the restoration of macropinocytosis and that aPKCs support PDAC growth in vivo. These results identify a previously unappreciated role for cell polarity proteins in the regulation of macropinocytosis and provide a better understanding of the mechanistic underpinnings that control macropinocytic uptake in the context of metabolic stress.
- Published
- 2024
- Full Text
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23. Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.
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Recouvreux MV, Grenier SF, Zhang Y, Esparza E, Lambies G, Galapate CM, Maganti S, Duong-Polk K, Bhullar D, Naeem R, Scott DA, Lowy AM, Tiriac H, and Commisso C
- Subjects
- Humans, Glutamine metabolism, Asparagine metabolism, Cell Line, Tumor, Asparaginase pharmacology, Neoplastic Processes, Pancreatic Neoplasms drug therapy, Carcinoma, Pancreatic Ductal drug therapy
- Abstract
In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine. As a metabolic adaptation, PDAC cells upregulate ASNS expression in response to DON, and we show that ASNS levels are inversely correlated with DON efficacy. We also show that L-asparaginase (ASNase) synergizes with DON to affect the viability of PDAC cells, and that DON and ASNase combination therapy has a significant impact on metastasis. These results shed light on the mechanisms that drive the effects of glutamine mimicry and point to the utility of cotargeting adaptive responses to control PDAC progression., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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- View/download PDF
24. A Mesenchymal Tumor Cell State Confers Increased Dependency on the BCL-XL Antiapoptotic Protein in Kidney Cancer.
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Grubb T, Maganti S, Krill-Burger JM, Fraser C, Stransky L, Radivoyevitch T, Sarosiek KA, Vazquez F, Kaelin WG, and Chakraborty AA
- Subjects
- Humans, Cell Line, Tumor, bcl-X Protein genetics, bcl-X Protein metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Apoptosis genetics, RNA, Small Interfering, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell genetics, Kidney Neoplasms drug therapy, Kidney Neoplasms genetics
- Abstract
Purpose: Advanced/metastatic forms of clear-cell renal cell carcinomas (ccRCC) have limited therapeutic options. Genome-wide genetic screens have identified cellular dependencies in many cancers. Using the Broad Institute/Novartis combined short hairpin RNA (shRNA) dataset, and cross-validation with the CRISPR/Cas9 DepMap (21Q3) dataset, we sought therapeutically actionable dependencies in kidney lineage cancers., Experimental Design: We identified preferential genetic dependencies in kidney cancer cells versus other lineages. BCL2L1, which encodes the BCL-XL antiapoptotic protein, scored as the top actionable dependency. We validated this finding using genetic and pharmacologic tools in a panel of ccRCC cell lines. Select BCL-XL-dependent (versus independent) cell lines were then transcriptionally profiled to identify biomarkers and mechanistic drivers of BCL-XL dependence. Cell-based studies (in vitro and in vivo) and clinical validations were used to address physiologic relevance., Results: Inactivation of BCL-XL, but not BCL-2, led to fitness defects in renal cancer cells, and sensitized them to chemotherapeutics. Transcriptomic profiling identified a "BCL-XL dependency" signature, including an elevated mesenchymal gene signature. A mesenchymal state was both necessary and sufficient to confer increased BCL-XL dependence. The "BCL-XL dependency" signature was observed in approximately 30% of human ccRCCs, which were also associated with worse clinical outcomes. Finally, an orally bioavailable BCL-XL inhibitor, A-1331852, showed antitumor efficacy in vivo., Conclusions: Our studies uncovered an unexpected link between cell state and BCL-XL dependence in ccRCC. Therapeutic agents that specifically target BCL-XL are available. Our work justifies testing the utility of BCL-XL blockade to target, likely, a clinically aggressive subset of human kidney cancers. See related commentary by Wang et al., p. 4600., (©2022 American Association for Cancer Research.)
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- 2022
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25. Treatment planning system commissioning of the first clinical biology-guided radiotherapy machine.
- Author
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Simiele E, Capaldi D, Breitkreutz D, Han B, Yeung T, White J, Zaks D, Owens M, Maganti S, Xing L, Surucu M, and Kovalchuk N
- Subjects
- Biology, Humans, Phantoms, Imaging, Radiometry methods, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: The RefleXion X1 is a novel radiotherapy machine designed for image-guided radiotherapy (IGRT) and biology-guided radiotherapy (BgRT). Its treatment planning system (TPS) generates IMRT and SBRT plans for a 6MV-FFF beam delivered axially via 50 firing positions with the couch advancing every 2.1 mm. The purpose of this work is to report the TPS commissioning results for the first clinical installation of RefleXion™ X1., Methods: CT images of multiple phantoms were imported into the RefleXion TPS to evaluate the accuracy of data transfer, anatomical modeling, plan evaluation, and dose calculation. Comparisons were made between the X1, Eclipse™, and MIM™. Dosimetric parameters for open static fields were evaluated in water and heterogeneous slab phantoms. Representative clinical IMRT and SBRT cases were planned and verified with ion chamber, film, and ArcCHECK
@ measurements. The agreement between TPS and measurements for various clinical plans was evaluated using Gamma analysis with a criterion of 3%/2 mm for ArcCHECK@ and film. End-to-end (E2E) testing was performed using anthropomorphic head and lung phantoms., Results: The average difference between the TPS-reported and known HU values was -1.4 ± 6.0 HU. For static fields, the agreements between the TPS-calculated and measured PDD10 , crossline profiles, and inline profiles (FWHM) were within 1.5%, 1.3%, and 0.5 mm, respectively. Measured output factors agreed with the TPS within 1.3%. Measured and calculated dose for static fields in heterogeneous phantoms agreed within 2.5%. The ArcCHECK@ mean absolute Gamma passing rate was 96.4% ± 3.4% for TG 119 and TG 244 plans and 97.8% ± 3.6% for the 21 clinical plans. E2E film analysis showed 0.8 mm total targeting error for isocentric and 1.1 mm for off-axis treatments., Conclusions: The TPS commissioning results of the RefleXion X1 TPS were within the tolerances specified by AAPM TG 53, MPPG 5.a, TG 119, and TG 148. A subset of the commissioning tests has been identified as baseline data for an ongoing QA program., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)- Published
- 2022
- Full Text
- View/download PDF
26. Machine Learning Methods for Identifying Critical Data Elements in Nursing Documentation.
- Author
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Bose E, Maganti S, Bowles KH, Brueshoff BL, and Monsen KA
- Subjects
- Documentation methods, Documentation statistics & numerical data, Electronic Health Records instrumentation, Electronic Health Records statistics & numerical data, Humans, Nurses, Public Health statistics & numerical data, Public Health Nursing methods, Public Health Nursing standards, Regression Analysis, Retrospective Studies, Common Data Elements standards, Documentation standards, Machine Learning, Nurses, Public Health standards
- Abstract
Background: Public health nurses (PHNs) engage in home visiting services and documentation of care services for at-risk clients. To increase efficiency and decrease documentation burden, it would be useful for PHNs to identify critical data elements most associated with patient care priorities and outcomes. Machine learning techniques can aid in retrospective identification of critical data elements., Objective: We used two different machine learning feature selection techniques of minimum redundancy-maximum relevance (mRMR) and LASSO (least absolute shrinkage and selection operator) and elastic net regularized generalized linear model (glmnet in R)., Methods: We demonstrated application of these techniques on the Omaha System database of 205 data elements (features) with a cohort of 756 family home visiting clients who received at least one visit from PHNs in a local Midwest public health agency. A dichotomous maternal risk index served as the outcome for feature selection., Application: Using mRMR as a feature selection technique, out of 206 features, 50 features were selected with scores greater than zero, and generalized linear model applied on the 50 features achieved highest accuracy of 86.2% on a held-out test set. Using glmnet as a feature selection technique and obtaining feature importance, 63 features had importance scores greater than zero, and generalized linear model applied on them achieved the highest accuracy of 95.5% on a held-out test set., Discussion: Feature selection techniques show promise toward reducing public health nursing documentation burden by identifying the most critical data elements needed to predict risk status. Further studies to refine the process of feature selection can aid in informing PHNs' focus on client-specific and targeted interventions in the delivery of care.
- Published
- 2019
- Full Text
- View/download PDF
27. Exploring Older Adults' Strengths, Problems, and Wellbeing Using De-identified Electronic Health Record Data.
- Author
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Gao G, Pieczkiewicz D, Kerr M, Lindquist R, Chi CL, Maganti S, Austin R, Kreitzer MJ, Todd K, and Monsen KA
- Subjects
- Aged, 80 and over, Assisted Living Facilities, Chronic Disease, Data Anonymization, Female, Humans, Male, Retrospective Studies, Vocabulary, Controlled, Aged, Electronic Health Records, Geriatric Assessment methods, Health Status
- Abstract
As new data sources including individuals' strengths emerge in electronic health records, such data provide whole-person oriented information to generate integrated knowledge for person-centered practice. The purpose of this study is to describe older adults' strengths and problems within a wellbeing context documented by the Omaha System. The Wellbeing Model is employed as a conceptual framework for wellbeing and is operationalized by the Omaha System Problem Classification Scheme. This study has a retrospective, descriptive design using de-identified EHR data of wellbeing assessments including problems, strengths, and signs/symptoms for a convenience sample of 440 assisted-living residents in a Midwest metropolitan area. Descriptive statistics and data visualization were used to summarize and display strength and signs/symptom attributes within wellbeing contexts. The study reveals cutting-edge knowledge regarding older adults' strengths and wellbeing, and creates a platform for further research use of a strength-based ontology in clinical practice and electronic system of documentation.
- Published
- 2018
28. Psychological Morbidity Among Dermatological Patients in a Rural Setting.
- Author
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Kosaraju SK, Reddy KS, Vadlamani N, Sandhya L, Kalasapati L, Maganti S, and Mary A
- Abstract
Background: Dermatological conditions have an impact on psychology of the patients. There is a dearth of studies regarding this field in Rural population of India., Aims and Objectives: The primary objective of this study is to evaluate the psychiatric morbidity in patients affected with Dermatological condition in a rural population and secondary objective is to assess the morbidity in dimensions of Depression Severity and the quality of life in the Emotional Sphere, Physical Symptoms, Psychosocial Functioning., Subjects and Methods: Seventy three rural patients were included in the study. PHQ9 and SKINDEX-29 was used to assess the psychiatric morbidity and quality of life. Statistical analysis was done using SPSS V 20. Chi-square test was used as a test of significance., Results: Significance has been found for duration of suffering from a dermatological condition and quality of life (p=0.03). Correlation has also been established between dermatological diagnosis with depression severity (p=0.004) or quality of life (p=0.004). In the sub scales of SKINDEX it was noted that overall dysfunction was notably more marked in Emotional Sphere and Psychosocial Functions than the Physical symptoms. Eczema was the most affected diagnosis in Skindex indicating a poor quality of life followed by psoriasis, Acne vulgaris and Seborrhoeic Dermatitis however, It was found that the majorly affected condition in depression severity was Psoriasis followed by Eczema, Acne Vulgaris and Seborrhoeic Dermatitis., Conclusion: There seems to be an increased morbidity among the rural population in depression severity and that of quality of life in terms of emotional sphere and psychosocial functioning.
- Published
- 2015
- Full Text
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29. Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models.
- Author
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Denis CV, Kwack K, Saffaripour S, Maganti S, André P, Schaub RG, and Wagner DD
- Subjects
- Animals, Bleeding Time, Cell Culture Techniques, Disease Models, Animal, Dose-Response Relationship, Drug, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Endothelium, Vascular metabolism, Factor VIII metabolism, Female, Heterozygote, Humans, Interleukin-11 administration & dosage, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, P-Selectin blood, P-Selectin drug effects, Platelet Count, Recombinant Proteins administration & dosage, Recombinant Proteins pharmacology, Time Factors, Umbilical Cord cytology, von Willebrand Factor genetics, von Willebrand Factor metabolism, Factor VIII drug effects, Interleukin-11 pharmacology, von Willebrand Diseases blood, von Willebrand Factor drug effects
- Abstract
Interleukin (IL)-11 is a cytokine with thrombopoietic activity that has been shown to increase plasma von Willebrand factor (vWf) in preliminary clinical studies. This led to further evaluation of the effect of recombinant human (rh)IL-11 on vWf and factor VIII (FVIII) secretion. In vitro, rhIL-11 did not increase vWf production by cultured endothelial cells, which suggests an indirect mechanism. Also, in vivo, plasma vWf was not elevated in mice shortly after a single intravenous (IV) bolus injection of 250 or 1000 microg/kg rhIL-11. The effect of continuous exposure to rhIL-11 was accessed by treating wild type mice for 7 consecutive days with subcutaneous 250 microg/kg/d rhIL-11. Platelet counts increased by 25% and 40% after 4 and 7 days, respectively. Plasma vWf and FVIII levels increased 2-fold after 4 and 7 days. Surprisingly, no effect of rhIL-11 on vWf or FVIII messenger RNA was observed, which suggests that the regulation by rhIL-11 occurs after transcription. No increase in soluble P-selectin was observed after rhIL-11 treatment, indicating that platelet activation is not the source of elevated vWf. Similarly to wild type mice, vWf heterozygous mice responded to rhIL-11 treatment by a significant increase in platelet counts and vWf and FVIII levels. Importantly, in vWf-deficient mice, rhIL-11 also induced a significant increase in FVIII independent of vWf and was able to reduce skin bleeding time. These results suggest that a clinical evaluation of the effects of rhIL-11-induced vWf/FVIII elevation in maintaining hemostasis in mild hemophilia A or von Willebrand disease would be worthwhile.
- Published
- 2001
- Full Text
- View/download PDF
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